Combination Study Of CP-751,871 With Paclitaxel And Carboplatin In Advanced Lung Cancer
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT00147537
Collaborator
(none)
282
31
2
77.9
9.1
0.1
Study Details
Study Description
Brief Summary
Phase 1b Dose Excalation/Expansion: Identify and characterize safety and tolerability of recommended phase 2 dose of CP-751,871 when administered with paclitaxel and carboplatin Phase 1b Erlotinib Extension: To characterize the safety and tolerability of CP751,871 when administered with paclitaxel, carboplatin and erlotinib.
Phase 2: To test the efficacy of CP-751,871 combined with paclitaxel and carboplatin in the treatment of advanced non-small cell lung cancer
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
282 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase 1b Dose Escalation/Phase 2 Randomized, Non-Comparative, Multiple Center, Open Label Study Of CP 751,871 In Combination With Paclitaxel And Carboplatin And Of Paclitaxel And Carboplatin Alone As First Line Treatment For Advanced Non-Small Cell Lung Cancer
Study Start Date
:
Feb 1, 2005
Actual Primary Completion Date
:
Aug 1, 2011
Actual Study Completion Date
:
Aug 1, 2011
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Phase 2 (Arms A & B) CP-751,871 + paclitaxel + carboplatin |
Drug: CP-751,871
Phase 2 Arm A:
CP-751,871 20 mg/kg IV over 2.5 hours up to 17 cycles
Drug: paclitaxel
Phase 2 Arm A:
Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles
Phase 2 Arm B:
Paclitaxel 200 mg/m2, IV over 3 hours up to 6 cycles
Drug: carboplatin
Phase 2 Arm A:
Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles
Phase 2 Arm B:
Carboplatin AUC 6, IV over 15-60 minutes up to 6 cycles
|
| Experimental: Phase 1b Phase 1b Dose Escalation /Expansion: CP-751,871 + paclitaxel + carboplatin Phase 1b Erlotinib Extension: CP-751,871 + paclitaxel + carboplatin + erlotinib |
Drug: CP-751,871
Phase 1b Dose Escalation/Expansion: CP-751,871 20 mg/kg IV over 2.5 hours (up to 17 cycles) Phase 1b Erlotinib Extension: CP-751,871 20 mg/kg IV over 2.5 hours (up to 17 cycles)
Drug: paclitaxel
Phase 1b Dose Escalation/Expansion: paclitaxel 200 mg/m2, IV over 3 hours (up to 6 cycles) Phase 1b Erlotinib Extension: paclitaxel 200 mg/m2, IV over 3 hours (up to 6 cycles)
Drug: carboplatin
Phase 1b Dose Escalation/Expansion: carboplatin AUC 6, IV over 15-60 minutes (up to 6 cycles) Phase 1b Erlotinib Extension: carboplatin AUC 6, IV over 15-60 minutes (up to 6 cycles)
Drug: erlotinib
Phase 1b Erlotinib Extension: erlotinib 150 mg/day orally every day (up to 17 cycles)
|
Outcome Measures
Primary Outcome Measures
- Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b [Start of treatment (baseline) up to the end of Cycle 1 (Day 21)]
The maximum tolerated dose of CP-751,871 in combination with paclitaxel and carboplatin is the highest dose level below the Maximum Administered Dose (the dose level at which 2 or more out of 3 to 6 patients experience a Dose Limiting Toxicity at a dose level in Cycle 1) at which none or one out of 6 patients experience a Cycle 1 Dose Limiting Toxicity.
- Recommended Phase 2 Dose (RP2D): Phase 1b [Start of treatment (baseline) up to the end of Cycle 1 (Day 21)]
- Objective Response Rate: Phase 2 [Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization]
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
- Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2 [Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization]
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
Secondary Outcome Measures
- Objective Response Rate: Phase 1b [Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization]
Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response.
- Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b [Day 1 pre-infusion of each cycle up to Cycle 17 (each cycle was 21 day), 150 days after the last CP-751,871 infusion, and last follow up visit (one year post last study dose)]
HAHA are indicators of immunogenicity to CP-751,871.
- Number of Circulating Endothelial Cells (CECs): Phase 1b [Day 1 pre-dose and Days 15 to 21 of Cycle 4]
- Number of Circulating Tumor-Related Cells (CTCs) and CTC Insulin-Like Growth Factor 1 Receptor (IGF-IR) Expression: Phase 1b [Day 1 pre-dose and Days 15 to 21 of Cycle 4]
Blood samples were collected to enumerate the number of total CTCs and CTC insulin-like growth factor 1 receptor (IGF-IR) expression
- Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b [Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)]
- Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b [Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)]
- Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 1 in Phase 1b [Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)]
AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504)
- Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 1b [Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)]
AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504)
- Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b [Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)]
AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time.
- Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b [Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b [Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half.
- CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b [Cycle 2 pre-infusion (which is the end of Cycle 1)]
Concentration at 504 hours post dose
- CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b [Cycle 5 pre-infusion (which is the end of Cycle 4)]
Concentration at 504 hours post dose
- Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b [Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1). Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).]
Accumulation ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b [Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
- Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b [Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)]
Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast)
- Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b [Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1)]
Maximum Observed Plasma Concentration
- Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b [Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is then end of Cycle 4)]
Maximum Observed Plasma Concentration
- Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2 [Day 1 pre-infusion of each Cycle (each cycle was 21 day) up to Cycle 17 and 150 days after the last CP-751,871 infusion]
HAHA are indicators of immunogenicity to CP-751,871
- M.D. Anderson Symptom Assessment Inventory (MDASI) in Phase 2 [Day 1 pre-dose of Cycle 1, weekly for Cycle 1 and 2, monthly prior to each subsequent cycle (Cycle 3 up to Cycle 17, each cycle was 21 day), and follow up (one year post last study dose)]
The MDASI is a 19-item questionnaire that assesses the severity of 13 symptoms over the past 24 hours, as well as how much the symptoms interfered with 6 areas of function (eg, walking, work, mood), when the symptom was "at its worst". Each item is scored from 0 to 10, with '0' indicating that the symptom was either not present or did not interfere with their activities, and '10' indicating that the symptom was "as bad as you can imagine" or "interfered completely" with their life. Total average score range: 0 to 10.
- The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC-QLQ-C30/-LC13) in Phase 2 [Day 1 pre-dose of Cycle 1, monthly prior to each cycle (up to 17 cycles, each cycle was 21 day), and follow up (one year post last study dose)]
The QLQ-C30/-LC13 is a 43 item, self-administered questionnaire designed to assess health outcomes in clinical trials. In addition to global quality of life, the measure assesses 5 functional domains (physical, role, cognitive, emotional and social functioning) and specific symptoms (eg, nausea, pain). Each item is rated on a 1-4 scale with '1' representing "not at all" and '4' "very much". Within domains, items are scored to obtain a total score with higher scores representative of poorer HRQoL. Scale score range: 0 to 100.
- Apparent Volume of CP-751,871 Distribution (Vd) for Cycle 4 in Phase 2 [Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4)]
Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed.
- Clearance (CL) of CP-751,871 for Cycle 4 in Phase 2 [Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).]
Systemic clearance.
- Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 2 [Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).]
AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504)
- CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 2 [Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).]
Concentration at 504 hours post dose
- Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 2 [Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4).]
Maximum Observed Plasma Concentration
- Progression-Free Survival (PFS): Phase 2 [Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization]
Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause whichever comes first. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]).
- Time to Progression (TTP) in Phase 2 [Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization]
Time in months from start of study treatment to first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]).
- Duration of Response (DR) in Phase 2 [Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization]
Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.44. DR was calculated for the subgroup of participants with a confirmed objective tumor response.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
- Diagnosis of advanced/metastatic lung cancer
Exclusion Criteria:
-
Previous treatment with chemotherapy
-
Uncontrolled diabetes
-
History/active cardiovascular disease
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Pfizer Investigational Site | Tucson | Arizona | United States | 85719 |
| 2 | Pfizer Investigational Site | Tucson | Arizona | United States | 85724-5024 |
| 3 | Pfizer Investigational Site | Tucson | Arizona | United States | 85724 |
| 4 | Pfizer Investigational Site | Greenbrae | California | United States | 94904 |
| 5 | Pfizer Investigational Site | Los Angeles | California | United States | 90048 |
| 6 | Pfizer Investigational Site | Jacksonville | Florida | United States | 32216 |
| 7 | Pfizer Investigational Site | Jacksonville | Florida | United States | 32224 |
| 8 | Pfizer Investigational Site | Jeffersonville | Indiana | United States | 47130 |
| 9 | Pfizer Investigational Site | Louisville | Kentucky | United States | 40202 |
| 10 | Pfizer Investigational Site | Louisville | Kentucky | United States | 40207 |
| 11 | Pfizer Investigational Site | Louisville | Kentucky | United States | 40217 |
| 12 | Pfizer Investigational Site | Louisville | Kentucky | United States | 40241 |
| 13 | Pfizer Investigational Site | Shelbyville | Kentucky | United States | 40065 |
| 14 | Pfizer Investigational Site | Baltimore | Maryland | United States | 21204 |
| 15 | Pfizer Investigational Site | Rochester | Minnesota | United States | 55905 |
| 16 | Pfizer Investigational Site | Corinth | Mississippi | United States | 38834 |
| 17 | Pfizer Investigational Site | Southaven | Mississippi | United States | 38671 |
| 18 | Pfizer Investigational Site | Creve Coeur | Missouri | United States | 63141 |
| 19 | Pfizer Investigational Site | St. Louis | Missouri | United States | 63110 |
| 20 | Pfizer Investigational Site | St. Peters | Missouri | United States | 63376 |
| 21 | Pfizer Investigational Site | Bronx | New York | United States | 10461 |
| 22 | Pfizer Investigational Site | Bronx | New York | United States | 10467 |
| 23 | Pfizer Investigational Site | Philadelphia | Pennsylvania | United States | 19111 |
| 24 | Pfizer Investigational Site | Memphis | Tennessee | United States | 38104 |
| 25 | Pfizer Investigational Site | Memphis | Tennessee | United States | 38120 |
| 26 | Pfizer Investigational Site | Houston | Texas | United States | 77030 |
| 27 | Pfizer Investigational Site | Montreal | Quebec | Canada | H3T 1E2 |
| 28 | Pfizer Investigational Site | Orbassano (TO) | Italy | 10043 | |
| 29 | Pfizer Investigational Site | L'hospitalet de Llobregat | Barcelona | Spain | 08907 |
| 30 | Pfizer Investigational Site | Madrid | Spain | 28041 | |
| 31 | Pfizer Investigational Site | Sevilla | Spain | 41013 |
Sponsors and Collaborators
- Pfizer
Investigators
- Study Director: Pfizer CT.gov Call Center, Pfizer
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00147537
Other Study ID Numbers:
- A4021002
First Posted:
Sep 7, 2005
Last Update Posted:
Oct 30, 2013
Last Verified:
Oct 1, 2013
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | CP-751,871 0.05 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) | CP-751,871(F)+Paclitaxel(P)+Carboplatin(C) (Phase 2) | Paclitaxel(P)+Carboplatin(C) (Phase 2) |
|---|---|---|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 (F) 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel (P) 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin (C) at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel (P) 200 mg/square meter (m^2) IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin (C) at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Period Title: Phase 1b | |||||||||||
| STARTED | 3 | 2 | 4 | 3 | 3 | 3 | 18 | 7 | 18 | 0 | 0 |
| COMPLETED | 1 | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 0 |
| NOT COMPLETED | 2 | 2 | 4 | 2 | 3 | 3 | 18 | 7 | 17 | 0 | 0 |
| Period Title: Phase 1b | |||||||||||
| STARTED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 166 | 55 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 5 | 3 |
| NOT COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 161 | 52 |
Baseline Characteristics
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) | Total |
|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05/0.1/0.8/1.5/3/6/10/20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Total of all reporting groups |
| Overall Participants | 43 | 18 | 166 | 55 | 282 |
| Age, Customized (participants) [Number] | |||||
| Less than 65 years old (<65) |
27
62.8%
|
13
72.2%
|
82
49.4%
|
33
60%
|
155
55%
|
| 65 to 69 years old (65 - 69) |
6
14%
|
2
11.1%
|
42
25.3%
|
11
20%
|
61
21.6%
|
| 70 years old and more than 70 years old (>=70) |
10
23.3%
|
2
11.1%
|
42
25.3%
|
11
20%
|
65
23%
|
| Unspecified |
0
0%
|
1
5.6%
|
0
0%
|
0
0%
|
1
0.4%
|
| Sex/Gender, Customized (participants) [Number] | |||||
| Female |
18
41.9%
|
8
44.4%
|
49
29.5%
|
21
38.2%
|
96
34%
|
| Male |
25
58.1%
|
9
50%
|
117
70.5%
|
34
61.8%
|
185
65.6%
|
| Unspecified |
0
0%
|
1
5.6%
|
0
0%
|
0
0%
|
1
0.4%
|
Outcome Measures
| Title | Maximum Tolerated Dose (MTD)of CP-751,871 in Combination With Paclitaxel and Carboplatin: Phase 1b |
|---|---|
| Description | The maximum tolerated dose of CP-751,871 in combination with paclitaxel and carboplatin is the highest dose level below the Maximum Administered Dose (the dose level at which 2 or more out of 3 to 6 patients experience a Dose Limiting Toxicity at a dose level in Cycle 1) at which none or one out of 6 patients experience a Cycle 1 Dose Limiting Toxicity. |
| Time Frame | Start of treatment (baseline) up to the end of Cycle 1 (Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of any agent. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) |
|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05/0.1/0.8/1.5/3/6/10/20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 42 |
| Number [mg/kg] |
NA
|
| Title | Recommended Phase 2 Dose (RP2D): Phase 1b |
|---|---|
| Description | |
| Time Frame | Start of treatment (baseline) up to the end of Cycle 1 (Day 21) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of any agent. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) |
|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05/0.1/0.8/1.5/3/6/10/20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 42 |
| Number [mg/kg] |
20
|
| Title | Objective Response Rate: Phase 2 |
|---|---|
| Description | Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. |
| Time Frame | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received any of the study treatments. N=number of participants who had measurable disease at baseline and an adequate baseline tumor assessment |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 99 | 51 |
| Number (90% Confidence Interval) [percentage of participants] |
37.4
87%
|
27.5
152.8%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) |
|---|---|---|
| Comments | A one-sided p-value for H0: objective response rate <=0.28 using exact binomial test at level 0.05. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.027 |
| Comments | ||
| Method | binomial test | |
| Comments | ||
| Title | Objective Response Rate in Non-Adenocarcinoma Participants: Phase 2 |
|---|---|
| Description | Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. |
| Time Frame | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received any of the study treatments. N=number of participants who had measurable disease at baseline and an adequate baseline tumor assessment |
| Arm/Group Title | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2) |
|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 73 |
| Number (90% Confidence Interval) [percentage of participants] |
37.0
86%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) |
|---|---|---|
| Comments | A One-sided p-value for H0: objective response rate <=0.30 using exact binomial test at level 0.05. | |
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | =0.121 |
| Comments | ||
| Method | binomial test | |
| Comments | ||
| Title | Objective Response Rate: Phase 1b |
|---|---|
| Description | Percentage of participants with objective response based on assessment of confirmed complete response (CR) or confirmed partial response (PR) according to Response Evaluation Criteria in Solid Tumor (RECIST). Confirmed CR defined as disappearance of all target lesions. Confirmed PR defined as ≥30% decrease in sum of the longest dimensions (LD) of the target lesions taking as a reference the baseline sum LD according to RECIST. Confirmed responses are those that persist on repeat imaging study ≥4 weeks after initial documentation of response. |
| Time Frame | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of any agent. N=number of participants who had measurable disease at baseline and an adequate baseline tumor assessment |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05/0.1/0.8/1.5/3/6/10/20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 36 | 16 |
| Number [percentage of participants] |
33.3
77.4%
|
25.0
138.9%
|
| Title | Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 1b |
|---|---|
| Description | HAHA are indicators of immunogenicity to CP-751,871. |
| Time Frame | Day 1 pre-infusion of each cycle up to Cycle 17 (each cycle was 21 day), 150 days after the last CP-751,871 infusion, and last follow up visit (one year post last study dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of any agent. N=number of participants who were analyzed for HAHA |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05/0.1/0.8/1.5/3/6/10/20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 21 | 8 |
| Number [number of participants] |
1
2.3%
|
0
0%
|
| Title | Number of Circulating Endothelial Cells (CECs): Phase 1b |
|---|---|
| Description | |
| Time Frame | Day 1 pre-dose and Days 15 to 21 of Cycle 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol amendment 6, blood samples for the rapid quantification of CECs were no longer collected from participants enrolled in the study. Insufficient data were available to evaluate for correlation. |
| Arm/Group Title | CP-751,871 0.05 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Number of Circulating Tumor-Related Cells (CTCs) and CTC Insulin-Like Growth Factor 1 Receptor (IGF-IR) Expression: Phase 1b |
|---|---|
| Description | Blood samples were collected to enumerate the number of total CTCs and CTC insulin-like growth factor 1 receptor (IGF-IR) expression |
| Time Frame | Day 1 pre-dose and Days 15 to 21 of Cycle 4 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Per protocol amendment 6, blood samples for the rapid quantification of CTCs were no longer collected from participants enrolled in the study. Insufficient data were available to evaluate for correlation. |
| Arm/Group Title | CP-751,871 0.05 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Title | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 1 in Phase 1b |
|---|---|
| Description | |
| Time Frame | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of Cycle 1 (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of Cycle 1 (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of Cycle 1 (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of Cycle 1 (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 1 | 4 | 3 | 3 | 3 | 14 | 6 | 16 |
| Mean (Standard Deviation) [milligram/liter (mg/L)] |
1.510
|
17.34
(10.28)
|
37.47
(9.0429)
|
75.17
(22.250)
|
147.3
(27.006)
|
261.3
(62.278)
|
415.7
(102.14)
|
485.0
(131.83)
|
| Title | Plasma Concentration of CP-751,871 at the End of Infusion (Cendinf) for Cycle 4 in Phase 1b |
|---|---|
| Description | |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of Cycle 1 (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of Cycle 1 (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of Cycle 1 (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of Cycle 1 (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 2 | 2 | 1 | 2 | 1 | 8 | 3 | 9 |
| Mean (Standard Deviation) [mg/L] |
2.975
(NA)
|
19.15
(NA)
|
40.70
|
100.7
(NA)
|
327.0
|
331.1
(125.77)
|
440.3
(211.67)
|
447.3
(210.19)
|
| Title | Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 1 in Phase 1b |
|---|---|
| Description | AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504) |
| Time Frame | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 1 | 4 | 1 | 2 | 2 | 10 | 5 | 17 |
| Mean (Standard Deviation) [milligram.hour/Liter (mg.hr/L)] |
22.30
|
2011
(1048.6)
|
5320
|
12810
(NA)
|
30500
(NA)
|
54650
(14075)
|
79820
(21767)
|
85240
(33973)
|
| Title | Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 1b |
|---|---|
| Description | AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504) |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 1 | 2 | 0 | 2 | 1 | 7 | 1 | 6 |
| Mean (Standard Deviation) [mg.hr/L] |
77.60
|
2410
(NA)
|
23200
(NA)
|
52500
|
94360
(11479)
|
214000
|
133200
(21292)
|
| Title | Area Under the Curve From Time Zero Extrapolated to Infinite Time [AUCinf] for CP-751,871 for Cycle 1 in Phase 1b |
|---|---|
| Description | AUCinf = Area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) extrapolated to infinite time. |
| Time Frame | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 3 | 0 | 2 | 1 | 4 | 1 | 7 |
| Mean (Standard Deviation) [mg.hr/L] |
1434
(914.58)
|
16750
(NA)
|
41200
|
69180
(10651)
|
12100
|
107400
(37604)
|
| Title | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 1 in Phase 1b |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 3 | 0 | 2 | 1 | 4 | 1 | 7 |
| Mean (Standard Deviation) [Day] |
2.84
(1.82)
|
10.81
(NA)
|
8.350
|
9.56
(2.02)
|
11.10
|
9.89
(1.81)
|
| Title | Plasma Decay Half-Life (t1/2) of CP-751,871 for Cycle 4 in Phase 1b |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 |
| Median (Standard Deviation) [Day] |
5.360
(NA)
|
15.40
|
| Title | CP-751,871 Concentration at 504 Hours Post Dose (C504) for Cycle 1 (End of the 21-day Cycle) in Phase 1b |
|---|---|
| Description | Concentration at 504 hours post dose |
| Time Frame | Cycle 2 pre-infusion (which is the end of Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 4 | 1 | 2 | 2 | 11 | 5 | 17 |
| Mean (Standard Deviation) [mg/L] |
0.1610
(0.3220)
|
4.550
|
9.820
(NA)
|
28.20
(NA)
|
61.11
(23.125)
|
95.20
(23.354)
|
86.73
(57.117)
|
| Title | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 1b |
|---|---|
| Description | Concentration at 504 hours post dose |
| Time Frame | Cycle 5 pre-infusion (which is the end of Cycle 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 1 | 2 | 0 | 2 | 1 | 7 | 1 | 7 |
| Mean (Standard Deviation) [mg/L] |
0.0000
|
0.4630
(NA)
|
27.70
(NA)
|
21.20
|
125.3
(16.101)
|
357.0
|
158.6
(27.067)
|
| Title | Accumulation of CP-751,871 Ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) in Phase 1b |
|---|---|
| Description | Accumulation ratio (Cycle 4 AUC504 / Cycle 1 AUC504) (Rac) |
| Time Frame | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1). Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 1 | 2 | 0 | 2 | 1 | 7 | 1 | 6 |
| Mean (Standard Deviation) [ratio] |
3.480
|
1.009
(NA)
|
1.830
(NA)
|
1.550
|
1.984
(0.3015)
|
2.260
|
1.962
(0.4283)
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871(AUClast) for Cycle 1 in Phase 1b |
|---|---|
| Description | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Time Frame | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter (mg/mL), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 1 | 4 | 3 | 3 | 3 | 12 | 6 | 17 |
| Mean (Standard Deviation) [mg.hr/L] |
16.60
|
1235
(713.55)
|
5137
(1682.5)
|
11350
(5551.7)
|
25630
(12536)
|
49260
(18770)
|
71200
(26855)
|
87680
(35247)
|
| Title | Area Under the Curve From Time Zero to Last Quantifiable Concentration of CP-751,871 (AUClast) for Cycle 4 in Phase 1b |
|---|---|
| Description | Area under the plasma concentration time-curve from zero to the last measured concentration (AUClast) |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 1 | 2 | 1 | 2 | 1 | 9 | 3 | 9 |
| Mean (Standard Deviation) [mg.hr/L] |
64.70
|
2255
(NA)
|
2670
|
23400
(NA)
|
70300
|
82930
(29539)
|
116200
(83683)
|
114000
(44197)
|
| Title | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 1 in Phase 1b |
|---|---|
| Description | Maximum Observed Plasma Concentration |
| Time Frame | Cycle 1 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 2 pre-infusion (which is the end of Cycle 1) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 1 | 4 | 3 | 3 | 3 | 14 | 6 | 17 |
| Mean (Standard Deviation) [mg/L] |
1.510
|
17.34
(10.280)
|
38.60
(10.989)
|
75.17
(22.250)
|
147.3
(27.006)
|
275.2
(89.932)
|
415.7
(102.14)
|
483.1
(128.14)
|
| Title | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 1b |
|---|---|
| Description | Maximum Observed Plasma Concentration |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hours and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is then end of Cycle 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least one dose of each agent. N=number of participants contributing to the summary statistics |
| Arm/Group Title | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 2 | 2 | 1 | 2 | 1 | 9 | 3 | 10 |
| Mean (Standard Deviation) [mg/L] |
2.975
(NA)
|
20.25
(NA)
|
40.70
|
100.7
(NA)
|
327.0
|
369.1
(91.602)
|
611.3
(43.501)
|
535.5
(180.97)
|
| Title | Number of Participants With Positive Human Anti-human Antibody (HAHA) Values: Phase 2 |
|---|---|
| Description | HAHA are indicators of immunogenicity to CP-751,871 |
| Time Frame | Day 1 pre-infusion of each Cycle (each cycle was 21 day) up to Cycle 17 and 150 days after the last CP-751,871 infusion |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received any of the study treatments. N=number of participants who were analyzed for HAHA |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin + Additional CP-751,871 (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 day cycle. Participants that were considered to be in stable disease after at least 4 cycles of treatment or in progressive disease at any time during the study could receive additional cycles of treatment with CP-751,871 in combination with Paclitaxel and Carboplatin or CP-751,871 alone. |
| Measure Participants | 38 | 4 |
| Number [number of participants] |
0
0%
|
0
0%
|
| Title | M.D. Anderson Symptom Assessment Inventory (MDASI) in Phase 2 |
|---|---|
| Description | The MDASI is a 19-item questionnaire that assesses the severity of 13 symptoms over the past 24 hours, as well as how much the symptoms interfered with 6 areas of function (eg, walking, work, mood), when the symptom was "at its worst". Each item is scored from 0 to 10, with '0' indicating that the symptom was either not present or did not interfere with their activities, and '10' indicating that the symptom was "as bad as you can imagine" or "interfered completely" with their life. Total average score range: 0 to 10. |
| Time Frame | Day 1 pre-dose of Cycle 1, weekly for Cycle 1 and 2, monthly prior to each subsequent cycle (Cycle 3 up to Cycle 17, each cycle was 21 day), and follow up (one year post last study dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the status of the program, no participants were analyzed for MDASI in phase 2. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 |
| Title | The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC-QLQ-C30/-LC13) in Phase 2 |
|---|---|
| Description | The QLQ-C30/-LC13 is a 43 item, self-administered questionnaire designed to assess health outcomes in clinical trials. In addition to global quality of life, the measure assesses 5 functional domains (physical, role, cognitive, emotional and social functioning) and specific symptoms (eg, nausea, pain). Each item is rated on a 1-4 scale with '1' representing "not at all" and '4' "very much". Within domains, items are scored to obtain a total score with higher scores representative of poorer HRQoL. Scale score range: 0 to 100. |
| Time Frame | Day 1 pre-dose of Cycle 1, monthly prior to each cycle (up to 17 cycles, each cycle was 21 day), and follow up (one year post last study dose) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the status of the program, no participants were analyzed for EORTC-QLQ-C30/-LC13 in phase 2. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 |
| Title | Apparent Volume of CP-751,871 Distribution (Vd) for Cycle 4 in Phase 2 |
|---|---|
| Description | Volume of distribution is defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Apparent volume of distribution after oral dose (Vz/F) is influenced by the fraction absorbed. |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4) |
Outcome Measure Data
| Analysis Population Description |
|---|
| Volume of distribution (Vd) was not calculated based on the status of the program and the limited value this further pharmacokinetic analyses would provide. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 |
| Title | Clearance (CL) of CP-751,871 for Cycle 4 in Phase 2 |
|---|---|
| Description | Systemic clearance. |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Clearance (CL) were not calculated based on the status of the program and the limited value this further PK analyses would provide. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 |
| Title | Area Under the Curve From Time Zero to 504 Hours [AUC (0-504)] Post Infusion of CP-751,871 for Cycle 4 in Phase 2 |
|---|---|
| Description | AUC (0-504)= Area under the plasma concentration versus time curve from time zero (pre-dose) to the end of the 21-day cycle, 504 hours(0-504) |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). |
Outcome Measure Data
| Analysis Population Description |
|---|
| AUC504 was not calculated for Cycle 4 in Phase 2 based on the status of the program and the limited value this further PK analyses would provide. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 |
| Title | CP-751,871 Concentration at 504 Hours Post Dose(C504) for Cycle 4 (End of the 21-day Cycle) in Phase 2 |
|---|---|
| Description | Concentration at 504 hours post dose |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). |
Outcome Measure Data
| Analysis Population Description |
|---|
| C504 was not calculated for Cycle 4 in Phase 2 based on the status of the program and the limited value this further PK analyses would provide. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 |
| Title | Maximum Observed Plasma CP-751,871 Concentration (Cmax) for Cycle 4 in Phase 2 |
|---|---|
| Description | Maximum Observed Plasma Concentration |
| Time Frame | Cycle 4 pre-infusion, 1 and 24 hour and 4 and 8 days post infusion, Cycle 5 pre-infusion (which is the end of Cycle 4). |
Outcome Measure Data
| Analysis Population Description |
|---|
| Cmax was not calculated for Cycle 4 in Phase 2 based on the status of the program and the limited value this further PK analyses would provide. |
| Arm/Group Title | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) |
|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 |
| Title | Progression-Free Survival (PFS): Phase 2 |
|---|---|
| Description | Time in months from start of study treatment to first documentation of objective tumor progression or death due to any cause whichever comes first. PFS was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]). |
| Time Frame | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received any of the study treatments. |
| Arm/Group Title | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 2) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2 NR) |
|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 mg/kg IV over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Phase 2 Non-Randomized (NR) Extension Cohort. Single intravenous (IV) dose of CP-751,871 20 mg/kg IV over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 58 | 49 | 56 | 56 |
| Median (90% Confidence Interval) [months] |
4.4
|
4.5
|
4.3
|
5.1
|
| Title | Time to Progression (TTP) in Phase 2 |
|---|---|
| Description | Time in months from start of study treatment to first documentation of objective tumor progression. TTP was calculated as (first event date minus the date of first dose of study medication plus 1) divided by 30.44. Tumor progression was determined from radiological image (where data meet the criteria for progressive disease [PD]). |
| Time Frame | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the status of the program, time to progression was not was not analyzed. |
| Arm/Group Title | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 2) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2 NR) |
|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 mg/kg IV over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Phase 2 Non-Randomized (NR) Extension Cohort. Single intravenous (IV) dose of CP-751,871 20 mg/kg IV over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 | 0 | 0 |
| Title | Duration of Response (DR) in Phase 2 |
|---|---|
| Description | Time in months from the first documentation of objective tumor response to objective tumor progression or death due to any cause. Duration of tumor response was calculated as (the date of the first documentation of objective tumor progression or death due to cancer minus the date of the first CR or PR that was subsequently confirmed plus 1) divided by 30.44. DR was calculated for the subgroup of participants with a confirmed objective tumor response. |
| Time Frame | Every 2 cycles (7 to 10 days prior to the planned start of the next cycle, each cycle was 21 days) from start of treatment until either death or a total of 2 years from the date of randomization |
Outcome Measure Data
| Analysis Population Description |
|---|
| Due to the status of the program, duration of response was not analyzed. |
| Arm/Group Title | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 2) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 2 NR) |
|---|---|---|---|---|
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 10 mg/kg IV over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Phase 2 Non-Randomized (NR) Extension Cohort. Single intravenous (IV) dose of CP-751,871 20 mg/kg IV over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. |
| Measure Participants | 0 | 0 | 0 | 0 |
Adverse Events
| Time Frame | ||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | The same event may appear as both an AE and a SAE. However, what is presented are distinct events. An event may be categorized as serious in one subject and as nonserious in another subject, or one subject may have experienced both a serious and nonserious event during the study. | |||||||||||||||||||||||
| Arm/Group Title | CP-751,871 0.05 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin + Additional CP-751,871 (Phase 2) | ||||||||||||
| Arm/Group Description | Single intravenous (IV) dose of CP-751,871 0.05 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.1 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 0.8 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 1.5 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 3 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 6 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each cycle (up to 1 year). Erlotinib 150 mg/day orally on Cycle 1 Day 1 (up to 1 year). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at a dose to attain the target area under the concentration-time curve (AUC) of 6 milligram/milliliter*minute (mg/mL*min), IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Single intravenous (IV) dose of CP-751,871 10 or 20 milligram/kilogram (mg/kg) over 2.5 hours on Day 1 of each Cycle (up to 17 cycles). Paclitaxel 200 mg/square meter (m^2), IV over 3 hours on Day 1 of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target area under the concentration-time curve (AUC) of 6 mg/mL*min, IV over 15-60 minutes on Day 1 of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL*min, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 days cycle. | Paclitaxel 200 mg/m^2 IV over 3 hours on Day 1 only of each cycle (up to 6 cycles) followed by carboplatin at dose to attain target AUC of 6 mg/mL, IV over 15-60 minutes on Day 1 only of each cycle (up to 6 cycles). Each cycle was 21 day cycle. Participants that were considered to be in stable disease after at least 4 cycles of treatment or in progressive disease at any time during the study could receive additional cycles of treatment with CP-751,871 in combination with Paclitaxel and Carboplatin or CP-751,871 alone. | ||||||||||||
All Cause Mortality |
||||||||||||||||||||||||
| CP-751,871 0.05 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin + Additional CP-751,871 (Phase 2) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | ||||||||||||
Serious Adverse Events |
||||||||||||||||||||||||
| CP-751,871 0.05 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin + Additional CP-751,871 (Phase 2) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/3 (0%) | 1/2 (50%) | 2/4 (50%) | 1/3 (33.3%) | 2/3 (66.7%) | 2/3 (66.7%) | 7/17 (41.2%) | 2/7 (28.6%) | 9/17 (52.9%) | 86/163 (52.8%) | 9/56 (16.1%) | 3/22 (13.6%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Febrile neutropenia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 8/163 (4.9%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Neutropenia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 5/163 (3.1%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Anaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Thrombocytopenia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||
| Acute myocardial infarction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Arrhythmia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Atrial fibrillation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Cardiogenic shock | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Mitral valve incompetence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Myocardial infarction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pericardial effusion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Tachycardia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tricuspid valve incompetence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Congenital, familial and genetic disorders | ||||||||||||||||||||||||
| Tracheo-oesophageal fistula | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Eye disorders | ||||||||||||||||||||||||
| Diplopia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Diarrhoea | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 2/17 (11.8%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Enteritis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Intestinal obstruction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nausea | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Vomiting | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 2/17 (11.8%) | 4/163 (2.5%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Abdominal pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Abdominal pain upper | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Constipation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dysphagia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gastrointestinal haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haematemesis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Intestinal perforation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pancreatitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pancreatitis acute | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Rectal haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| General disorders | ||||||||||||||||||||||||
| Disease progression | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 3/17 (17.6%) | 11/163 (6.7%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Mucosal haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Performance status decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pyrexia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 4/163 (2.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Asthenia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Chest pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Death | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Fatigue | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| General physical health deterioration | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Mucosal inflammation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Multi-organ failure | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Immune system disorders | ||||||||||||||||||||||||
| Anaphylactic reaction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Infections and infestations | ||||||||||||||||||||||||
| Cellulitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Device related infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Pneumonia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 7/163 (4.3%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Abdominal sepsis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Clostridial infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Diverticulitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Lobar pneumonia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pneumonia necrotising | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Rectal abscess | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Respiratory tract infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Sepsis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Staphylococcal infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tooth abscess | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Urosepsis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Fall | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Femur fracture | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Investigations | ||||||||||||||||||||||||
| Oxygen saturation decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haemoglobin decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Platelet count decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Dehydration | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/17 (17.6%) | 0/7 (0%) | 0/17 (0%) | 12/163 (7.4%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Failure to thrive | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyperglycaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 11/163 (6.7%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Decreased appetite | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Diabetes mellitus | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Diabetic complication | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypercalcaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypoglycaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyponatraemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 4/163 (2.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypophagia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Back pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Fistula | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Muscular weakness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pain in extremity | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||||||||||||
| Metastases to meninges | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cancer pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Malignant pleural effusion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Non-small cell lung cancer | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||
| Cerebrovascular accident | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Depressed level of consciousness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hydrocephalus | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cerebral ischaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Convulsion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Dizziness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Epilepsy | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Peripheral sensory neuropathy | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Somnolence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||
| Confusional state | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Major depression | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Suicidal ideation | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Catatonia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Completed suicide | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Delirium | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Depression | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Mental status changes | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Personality disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||
| Renal failure acute | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Incontinence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Renal failure | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Dyspnoea | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 6/163 (3.7%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Epistaxis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pleural effusion | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Pulmonary embolism | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 6/163 (3.7%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Chronic obstructive pulmonary disease | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Cough | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dysphonia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haemoptysis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypoxia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pneumothorax | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Respiratory failure | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Leukocytoclastic vasculitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Purpura | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Vascular disorders | ||||||||||||||||||||||||
| Embolism | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Orthostatic hypotension | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Deep vein thrombosis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Thrombosis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Vasculitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||||||||||||
| CP-751,871 0.05 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.1 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 0.8 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 1.5 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 3 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 6 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 10 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 20 mg/kg + Paclitaxel + Carboplatin (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin + Erlotinib (Phase 1b) | CP-751,871 + Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin (Phase 2) | Paclitaxel + Carboplatin + Additional CP-751,871 (Phase 2) | |||||||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/3 (100%) | 2/2 (100%) | 4/4 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 17/17 (100%) | 7/7 (100%) | 17/17 (100%) | 162/163 (99.4%) | 55/56 (98.2%) | 22/22 (100%) | ||||||||||||
| Blood and lymphatic system disorders | ||||||||||||||||||||||||
| Anaemia | 0/3 (0%) | 1/2 (50%) | 1/4 (25%) | 0/3 (0%) | 2/3 (66.7%) | 0/3 (0%) | 1/17 (5.9%) | 4/7 (57.1%) | 9/17 (52.9%) | 56/163 (34.4%) | 15/56 (26.8%) | 4/22 (18.2%) | ||||||||||||
| Leukopenia | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 2/17 (11.8%) | 13/163 (8%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Neutropenia | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 3/3 (100%) | 1/3 (33.3%) | 6/17 (35.3%) | 0/7 (0%) | 6/17 (35.3%) | 52/163 (31.9%) | 13/56 (23.2%) | 1/22 (4.5%) | ||||||||||||
| Thrombocytopenia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 2/7 (28.6%) | 4/17 (23.5%) | 43/163 (26.4%) | 12/56 (21.4%) | 3/22 (13.6%) | ||||||||||||
| Febrile neutropenia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Leukocytosis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Lymph node pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Lymphadenopathy | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Cardiac disorders | ||||||||||||||||||||||||
| Bradycardia | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cardiac failure congestive | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Cyanosis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Extrasystoles | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Left ventricular dysfunction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Pericardial effusion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tachycardia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Angina pectoris | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Arrhythmia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Atrial fibrillation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Cardiac tamponade | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Intracardiac thrombus | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nodal arrhythmia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Palpitations | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ventricular tachycardia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Congenital, familial and genetic disorders | ||||||||||||||||||||||||
| Phimosis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ear and labyrinth disorders | ||||||||||||||||||||||||
| Ear congestion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ear disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Hearing impaired | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypoacusis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 7/163 (4.3%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tinnitus | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/17 (5.9%) | 1/7 (14.3%) | 0/17 (0%) | 8/163 (4.9%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Vertigo | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Cerumen impaction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Deafness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 6/163 (3.7%) | 0/56 (0%) | 2/22 (9.1%) | ||||||||||||
| Ear discomfort | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ear pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Vestibular disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Endocrine disorders | ||||||||||||||||||||||||
| Hypothyroidism | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Eye disorders | ||||||||||||||||||||||||
| Blepharospasm | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Chalazion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Conjunctivitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Dry eye | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 4/163 (2.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Eye disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Eye irritation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Eye pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Eye swelling | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Lacrimation increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ocular hyperaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Vision blurred | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/17 (11.8%) | 1/7 (14.3%) | 0/17 (0%) | 4/163 (2.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Visual impairment | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Xerophthalmia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blindness unilateral | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cataract | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Diplopia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Visual acuity reduced | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gastrointestinal disorders | ||||||||||||||||||||||||
| Abdominal discomfort | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Abdominal distension | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Abdominal pain | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 1/7 (14.3%) | 1/17 (5.9%) | 17/163 (10.4%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Abdominal pain lower | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Abdominal pain upper | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 3/163 (1.8%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Abdominal tenderness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Aphthous stomatitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cheilitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Constipation | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 5/17 (29.4%) | 0/7 (0%) | 2/17 (11.8%) | 49/163 (30.1%) | 17/56 (30.4%) | 5/22 (22.7%) | ||||||||||||
| Diarrhoea | 1/3 (33.3%) | 0/2 (0%) | 2/4 (50%) | 0/3 (0%) | 2/3 (66.7%) | 2/3 (66.7%) | 9/17 (52.9%) | 3/7 (42.9%) | 11/17 (64.7%) | 65/163 (39.9%) | 12/56 (21.4%) | 5/22 (22.7%) | ||||||||||||
| Dry mouth | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 11/163 (6.7%) | 6/56 (10.7%) | 1/22 (4.5%) | ||||||||||||
| Dyspepsia | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 1/3 (33.3%) | 2/3 (66.7%) | 1/3 (33.3%) | 4/17 (23.5%) | 1/7 (14.3%) | 0/17 (0%) | 19/163 (11.7%) | 5/56 (8.9%) | 3/22 (13.6%) | ||||||||||||
| Dysphagia | 2/3 (66.7%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/17 (5.9%) | 0/7 (0%) | 3/17 (17.6%) | 15/163 (9.2%) | 1/56 (1.8%) | 2/22 (9.1%) | ||||||||||||
| Faecal incontinence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Flatulence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 7/163 (4.3%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Gastrointestinal pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gastrooesophageal reflux disease | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gingival pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 1/7 (14.3%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haemorrhoids | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 7/163 (4.3%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Melaena | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Mucous stools | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nausea | 1/3 (33.3%) | 1/2 (50%) | 1/4 (25%) | 0/3 (0%) | 3/3 (100%) | 0/3 (0%) | 10/17 (58.8%) | 2/7 (28.6%) | 11/17 (64.7%) | 84/163 (51.5%) | 24/56 (42.9%) | 1/22 (4.5%) | ||||||||||||
| Odynophagia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Oral pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Proctalgia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Rectal haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 5/163 (3.1%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Regurgitation | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Retching | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Stomatitis | 2/3 (66.7%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 4/17 (23.5%) | 1/7 (14.3%) | 7/17 (41.2%) | 30/163 (18.4%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Toothache | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 1/17 (5.9%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Vomiting | 0/3 (0%) | 1/2 (50%) | 2/4 (50%) | 0/3 (0%) | 2/3 (66.7%) | 0/3 (0%) | 5/17 (29.4%) | 2/7 (28.6%) | 9/17 (52.9%) | 48/163 (29.4%) | 11/56 (19.6%) | 1/22 (4.5%) | ||||||||||||
| Anal fissure | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ascites | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Breath odour | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Dental plaque | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Diverticulum | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Duodenogastric reflux | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Gastritis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gastrointestinal disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gingival bleeding | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Gingival disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gingivitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Glossitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haematemesis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haemorrhoidal haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hiatus hernia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Mouth ulceration | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Oesophageal food impaction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Oesophagitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Perianal erythema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Periodontal disease | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Steatorrhoea | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tongue discolouration | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tooth loss | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| General disorders | ||||||||||||||||||||||||
| Adverse drug reaction | 0/3 (0%) | 1/2 (50%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Asthenia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 4/17 (23.5%) | 1/7 (14.3%) | 6/17 (35.3%) | 27/163 (16.6%) | 5/56 (8.9%) | 1/22 (4.5%) | ||||||||||||
| Catheter site pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Chest discomfort | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Chest pain | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 2/7 (28.6%) | 1/17 (5.9%) | 18/163 (11%) | 1/56 (1.8%) | 2/22 (9.1%) | ||||||||||||
| Chills | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Fatigue | 3/3 (100%) | 2/2 (100%) | 1/4 (25%) | 3/3 (100%) | 3/3 (100%) | 2/3 (66.7%) | 10/17 (58.8%) | 5/7 (71.4%) | 8/17 (47.1%) | 107/163 (65.6%) | 26/56 (46.4%) | 14/22 (63.6%) | ||||||||||||
| Feeling cold | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gait disturbance | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 2/22 (9.1%) | ||||||||||||
| General physical health deterioration | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Infusion site pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Malaise | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Mucosal inflammation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/17 (17.6%) | 0/7 (0%) | 8/17 (47.1%) | 27/163 (16.6%) | 5/56 (8.9%) | 2/22 (9.1%) | ||||||||||||
| Nodule | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Oedema peripheral | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 6/163 (3.7%) | 6/56 (10.7%) | 5/22 (22.7%) | ||||||||||||
| Pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 17/163 (10.4%) | 7/56 (12.5%) | 2/22 (9.1%) | ||||||||||||
| Pyrexia | 1/3 (33.3%) | 0/2 (0%) | 1/4 (25%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 2/17 (11.8%) | 24/163 (14.7%) | 7/56 (12.5%) | 1/22 (4.5%) | ||||||||||||
| Axillary pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Catheter site haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Disease progression | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Extravasation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gravitational oedema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Infusion site reaction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Infusion site swelling | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Local swelling | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Non-cardiac chest pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Oedema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 4/56 (7.1%) | 2/22 (9.1%) | ||||||||||||
| Temperature intolerance | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 4/163 (2.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hepatobiliary disorders | ||||||||||||||||||||||||
| Hepatomegaly | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Hyperbilirubinaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Immune system disorders | ||||||||||||||||||||||||
| Drug hypersensitivity | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Multiple allergies | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypersensitivity | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Infections and infestations | ||||||||||||||||||||||||
| Bronchitis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Bronchopneumonia | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ear infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Empyema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gastrointestinal viral infection | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Herpes zoster | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Infection | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 17/163 (10.4%) | 2/56 (3.6%) | 3/22 (13.6%) | ||||||||||||
| Laryngitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Localised infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Lung infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nasopharyngitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 1/17 (5.9%) | 8/163 (4.9%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Oral candidiasis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 6/163 (3.7%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Oral fungal infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pharyngitis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pneumonia 1 | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Rhinitis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 7/163 (4.3%) | 7/56 (12.5%) | 5/22 (22.7%) | ||||||||||||
| Sinusitis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 4/163 (2.5%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Skin infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tooth infection | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Upper respiratory tract infection | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 6/163 (3.7%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Urinary tract infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 0/7 (0%) | 4/17 (23.5%) | 8/163 (4.9%) | 1/56 (1.8%) | 2/22 (9.1%) | ||||||||||||
| Abscess limb | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Breast abscess | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Candidiasis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Cellulitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Clostridium difficile colitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cystitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dermatitis infected | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Device related infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Diverticulitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ear lobe infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Folliculitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Gastroenteritis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Gastroenteritis viral | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Herpes simplex | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Hordeolum | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Oesophageal candidiasis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Oral herpes | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Oral infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Otitis externa | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Respiratory tract infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tinea pedis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tonsillitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Tooth abscess | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Vulvovaginal mycotic infection | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Injury, poisoning and procedural complications | ||||||||||||||||||||||||
| Contusion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 5/163 (3.1%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Excoriation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Laceration | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Peroneal nerve injury | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Animal bite | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Fall | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Femur fracture | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Hip fracture | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Lower limb fracture | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Post procedural diarrhoea | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Procedural nausea | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Procedural vomiting | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tooth fracture | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Wound | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Investigations | ||||||||||||||||||||||||
| Alanine aminotransferase | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Alanine aminotransferase increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 16/163 (9.8%) | 2/56 (3.6%) | 2/22 (9.1%) | ||||||||||||
| Aspartate aminotransferase | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Aspartate aminotransferase increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 10/163 (6.1%) | 2/56 (3.6%) | 1/22 (4.5%) | ||||||||||||
| Blood alkaline phosphatase | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Blood bicarbonate decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 4/17 (23.5%) | 3/163 (1.8%) | 2/56 (3.6%) | 3/22 (13.6%) | ||||||||||||
| Blood bilirubin increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood calcium decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood chloride decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 5/163 (3.1%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood creatinine | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood creatinine increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 3/17 (17.6%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood lactate dehydrogenase | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood magnesium decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 11/163 (6.7%) | 6/56 (10.7%) | 5/22 (22.7%) | ||||||||||||
| Blood phosphorus decreased | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Blood phosphorus increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 4/163 (2.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood potassium increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood urea increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 1/17 (5.9%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood uric acid increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 10/163 (6.1%) | 0/56 (0%) | 2/22 (9.1%) | ||||||||||||
| Gamma-glutamyltransferase | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Gamma-glutamyltransferase increased | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 27/163 (16.6%) | 6/56 (10.7%) | 2/22 (9.1%) | ||||||||||||
| Haemoglobin | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 5/163 (3.1%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haemoglobin decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 1/7 (14.3%) | 4/17 (23.5%) | 10/163 (6.1%) | 4/56 (7.1%) | 4/22 (18.2%) | ||||||||||||
| Neutrophil count decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 3/17 (17.6%) | 5/163 (3.1%) | 4/56 (7.1%) | 1/22 (4.5%) | ||||||||||||
| Neutrophil count increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Platelet count decreased | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 2/17 (11.8%) | 0/7 (0%) | 5/17 (29.4%) | 9/163 (5.5%) | 4/56 (7.1%) | 3/22 (13.6%) | ||||||||||||
| Prothrombin time prolonged | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Troponin | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Weight decreased | 0/3 (0%) | 1/2 (50%) | 2/4 (50%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 5/17 (29.4%) | 1/7 (14.3%) | 6/17 (35.3%) | 35/163 (21.5%) | 2/56 (3.6%) | 4/22 (18.2%) | ||||||||||||
| Weight increased | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| White blood cell count decreased | 2/3 (66.7%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 3/17 (17.6%) | 4/163 (2.5%) | 3/56 (5.4%) | 1/22 (4.5%) | ||||||||||||
| White blood cell count increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Activated partial thromboplastin time | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Bacterial test positive | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood albumin decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 2/56 (3.6%) | 1/22 (4.5%) | ||||||||||||
| Blood alkaline phosphatase decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 12/163 (7.4%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Blood chloride increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood creatine phosphokinase increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood creatinine increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 21/163 (12.9%) | 1/56 (1.8%) | 2/22 (9.1%) | ||||||||||||
| Blood glucose increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Blood immunoglobulin G increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood lactate dehydrogenase increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Blood magnesium increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood potassium decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood pressure increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blood sodium decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Blood urine present | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Coagulation test abnormal | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Fungal test positive | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Glucose urine | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haematocrit | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haematocrit decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| International normalised ratio increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| International normalised ratio normal | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Neutrophil count | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 4/163 (2.5%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Occult blood positive | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Platelet count | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Protein total increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Protein urine present | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Red blood cell count decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Red blood cell sedimentation rate | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Troponin I | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Troponin I increased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Urinary casts | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Urine leukocyte esterase | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| White blood cell count | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 2/56 (3.6%) | 1/22 (4.5%) | ||||||||||||
| Metabolism and nutrition disorders | ||||||||||||||||||||||||
| Cachexia | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Decreased appetite | 1/3 (33.3%) | 1/2 (50%) | 2/4 (50%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 9/17 (52.9%) | 2/7 (28.6%) | 8/17 (47.1%) | 69/163 (42.3%) | 15/56 (26.8%) | 9/22 (40.9%) | ||||||||||||
| Dehydration | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 2/17 (11.8%) | 1/7 (14.3%) | 2/17 (11.8%) | 14/163 (8.6%) | 2/56 (3.6%) | 2/22 (9.1%) | ||||||||||||
| Gout | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypercalcaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 6/163 (3.7%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Hypercholesterolaemia | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyperglycaemia | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 2/3 (66.7%) | 6/17 (35.3%) | 3/7 (42.9%) | 11/17 (64.7%) | 67/163 (41.1%) | 9/56 (16.1%) | 8/22 (36.4%) | ||||||||||||
| Hypermagnesaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyperuricaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 10/163 (6.1%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Hypoalbuminaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 3/17 (17.6%) | 2/163 (1.2%) | 1/56 (1.8%) | 2/22 (9.1%) | ||||||||||||
| Hypocalcaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 2/17 (11.8%) | 3/163 (1.8%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Hypokalaemia | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 2/17 (11.8%) | 9/163 (5.5%) | 3/56 (5.4%) | 1/22 (4.5%) | ||||||||||||
| Hypomagnesaemia | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 2/7 (28.6%) | 3/17 (17.6%) | 6/163 (3.7%) | 4/56 (7.1%) | 5/22 (22.7%) | ||||||||||||
| Hyponatraemia | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 6/17 (35.3%) | 17/163 (10.4%) | 2/56 (3.6%) | 4/22 (18.2%) | ||||||||||||
| Hyperkalaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 11/163 (6.7%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyperlipidaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypernatraemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Hyperphagia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypertriglyceridaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypoglycaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypophosphataemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Hypouricaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Increased appetite | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Polydipsia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Type 2 diabetes mellitus | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||||||||||||
| Arthralgia | 3/3 (100%) | 1/2 (50%) | 1/4 (25%) | 1/3 (33.3%) | 0/3 (0%) | 2/3 (66.7%) | 6/17 (35.3%) | 3/7 (42.9%) | 8/17 (47.1%) | 48/163 (29.4%) | 18/56 (32.1%) | 7/22 (31.8%) | ||||||||||||
| Arthropathy | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Back pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 1/17 (5.9%) | 1/7 (14.3%) | 1/17 (5.9%) | 25/163 (15.3%) | 4/56 (7.1%) | 2/22 (9.1%) | ||||||||||||
| Bone pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 7/163 (4.3%) | 2/56 (3.6%) | 2/22 (9.1%) | ||||||||||||
| Flank pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Lower extremity mass | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Muscle rigidity | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Muscle spasms | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 3/17 (17.6%) | 2/7 (28.6%) | 4/17 (23.5%) | 15/163 (9.2%) | 3/56 (5.4%) | 1/22 (4.5%) | ||||||||||||
| Muscle twitching | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Muscular weakness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 4/163 (2.5%) | 7/56 (12.5%) | 3/22 (13.6%) | ||||||||||||
| Musculoskeletal chest pain | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 1/7 (14.3%) | 0/17 (0%) | 2/163 (1.2%) | 2/56 (3.6%) | 1/22 (4.5%) | ||||||||||||
| Musculoskeletal pain | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/17 (5.9%) | 2/7 (28.6%) | 3/17 (17.6%) | 18/163 (11%) | 4/56 (7.1%) | 4/22 (18.2%) | ||||||||||||
| Myalgia | 3/3 (100%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 3/17 (17.6%) | 2/7 (28.6%) | 7/17 (41.2%) | 32/163 (19.6%) | 13/56 (23.2%) | 5/22 (22.7%) | ||||||||||||
| Pain in extremity | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 2/3 (66.7%) | 1/3 (33.3%) | 1/3 (33.3%) | 4/17 (23.5%) | 0/7 (0%) | 1/17 (5.9%) | 27/163 (16.6%) | 6/56 (10.7%) | 4/22 (18.2%) | ||||||||||||
| Tendonitis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Arthritis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 4/163 (2.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Jaw disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Joint effusion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Muscle atrophy | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Musculoskeletal disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Musculoskeletal stiffness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Myopathy | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Neck pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pain in jaw | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Plantar fasciitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Nervous system disorders | ||||||||||||||||||||||||
| Ataxia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Balance disorder | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cerebral disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cognitive disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Convulsion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dizziness | 2/3 (66.7%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 3/7 (42.9%) | 4/17 (23.5%) | 27/163 (16.6%) | 4/56 (7.1%) | 4/22 (18.2%) | ||||||||||||
| Dysgeusia | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 5/17 (29.4%) | 4/7 (57.1%) | 5/17 (29.4%) | 43/163 (26.4%) | 7/56 (12.5%) | 6/22 (27.3%) | ||||||||||||
| Headache | 2/3 (66.7%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/17 (11.8%) | 0/7 (0%) | 2/17 (11.8%) | 30/163 (18.4%) | 2/56 (3.6%) | 4/22 (18.2%) | ||||||||||||
| Hemiparesis | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hydrocephalus | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyperaesthesia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypoaesthesia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 1/7 (14.3%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Motor dysfunction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Neuropathy peripheral | 1/3 (33.3%) | 1/2 (50%) | 2/4 (50%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 6/17 (35.3%) | 3/7 (42.9%) | 4/17 (23.5%) | 57/163 (35%) | 22/56 (39.3%) | 14/22 (63.6%) | ||||||||||||
| Neurotoxicity | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nystagmus | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Paraesthesia | 1/3 (33.3%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 1/7 (14.3%) | 0/17 (0%) | 16/163 (9.8%) | 4/56 (7.1%) | 1/22 (4.5%) | ||||||||||||
| Parosmia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Peripheral sensory neuropathy | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/17 (17.6%) | 0/7 (0%) | 5/17 (29.4%) | 38/163 (23.3%) | 10/56 (17.9%) | 2/22 (9.1%) | ||||||||||||
| Peroneal nerve palsy | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Psychomotor hyperactivity | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Sensory disturbance | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Sensory loss | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Somnolence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Syncope | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 5/163 (3.1%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Tremor | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 4/163 (2.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Visual field defect | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ageusia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Amnesia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Anosmia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Aphasia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Brain oedema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cerebral ischaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Depressed level of consciousness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dizziness postural | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dysaesthesia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dysarthria | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dyskinesia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 2/56 (3.6%) | 1/22 (4.5%) | ||||||||||||
| Essential tremor | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypokinesia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyposmia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Memory impairment | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Neuralgia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Peripheral motor neuropathy | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Presyncope | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tonic convulsion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Vocal cord paralysis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Psychiatric disorders | ||||||||||||||||||||||||
| Anxiety | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 1/3 (33.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 9/163 (5.5%) | 4/56 (7.1%) | 1/22 (4.5%) | ||||||||||||
| Confusional state | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 0/7 (0%) | 1/17 (5.9%) | 7/163 (4.3%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Depression | 1/3 (33.3%) | 2/2 (100%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 1/17 (5.9%) | 0/7 (0%) | 2/17 (11.8%) | 5/163 (3.1%) | 2/56 (3.6%) | 2/22 (9.1%) | ||||||||||||
| Insomnia | 1/3 (33.3%) | 1/2 (50%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 4/17 (23.5%) | 0/7 (0%) | 0/17 (0%) | 13/163 (8%) | 4/56 (7.1%) | 3/22 (13.6%) | ||||||||||||
| Mood altered | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Restlessness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Vocal cord paralysis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Libido decreased | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Mental status changes | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Psychotic disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Stress | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Renal and urinary disorders | ||||||||||||||||||||||||
| Dysuria | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 9/163 (5.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haematuria | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pollakiuria | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Proteinuria | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Urinary incontinence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 5/163 (3.1%) | 0/56 (0%) | 2/22 (9.1%) | ||||||||||||
| Urinary retention | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Urogenital haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Bladder spasm | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Micturition disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Micturition urgency | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nocturia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Polyuria | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Renal colic | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Stress urinary incontinence | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Urethral haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Urinary hesitation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Reproductive system and breast disorders | ||||||||||||||||||||||||
| Erectile dysfunction | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pelvic pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Scrotal erythema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Genital rash | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Prostatitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Vaginal haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||||||||||||
| Atelectasis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Cough | 1/3 (33.3%) | 1/2 (50%) | 0/4 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 4/17 (23.5%) | 2/7 (28.6%) | 3/17 (17.6%) | 35/163 (21.5%) | 7/56 (12.5%) | 7/22 (31.8%) | ||||||||||||
| Dry throat | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dysphonia | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 9/163 (5.5%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Dyspnoea | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 2/3 (66.7%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 3/7 (42.9%) | 5/17 (29.4%) | 40/163 (24.5%) | 15/56 (26.8%) | 5/22 (22.7%) | ||||||||||||
| Dyspnoea exertional | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Epistaxis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 0/7 (0%) | 5/17 (29.4%) | 26/163 (16%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Haemoptysis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 20/163 (12.3%) | 1/56 (1.8%) | 2/22 (9.1%) | ||||||||||||
| Hiccups | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Hypoxia | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 1/17 (5.9%) | 3/163 (1.8%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Nasal congestion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 5/163 (3.1%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Oropharyngeal pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 2/17 (11.8%) | 4/163 (2.5%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Pleural effusion | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Pneumothorax | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Productive cough | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 6/163 (3.7%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Pulmonary embolism | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pulmonary hypertension | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Rhinorrhoea | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/17 (11.8%) | 1/7 (14.3%) | 0/17 (0%) | 5/163 (3.1%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Sinus congestion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Sinus disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Sneezing | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Sputum discoloured | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tachypnoea | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Upper-airway cough syndrome | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Wheezing | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Asthma | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Bronchospasm | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Chronic obstructive pulmonary disease | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Nasal disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nasal ulcer | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Painful respiration | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Paranasal sinus hypersecretion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pleuritic pain | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pulmonary haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Respiratory distress | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Respiratory tract congestion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Respiratory tract haemorrhage | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Rhinitis allergic | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||||||||||||
| Acne | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Alopecia | 3/3 (100%) | 2/2 (100%) | 1/4 (25%) | 2/3 (66.7%) | 3/3 (100%) | 3/3 (100%) | 10/17 (58.8%) | 3/7 (42.9%) | 10/17 (58.8%) | 91/163 (55.8%) | 31/56 (55.4%) | 15/22 (68.2%) | ||||||||||||
| Dermatitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dry skin | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 6/17 (35.3%) | 2/7 (28.6%) | 7/17 (41.2%) | 10/163 (6.1%) | 4/56 (7.1%) | 2/22 (9.1%) | ||||||||||||
| Eczema | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Erythema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 3/163 (1.8%) | 2/56 (3.6%) | 1/22 (4.5%) | ||||||||||||
| Hair growth abnormal | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hair texture abnormal | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hirsutism | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyperhidrosis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 2/56 (3.6%) | 1/22 (4.5%) | ||||||||||||
| Ingrowing nail | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 2/17 (11.8%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nail disorder | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 9/163 (5.5%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Nail toxicity | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Palmar erythema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Palmar-plantar erythrodysaesthesia syndrome | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Petechiae | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pruritus | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 3/17 (17.6%) | 0/7 (0%) | 1/17 (5.9%) | 8/163 (4.9%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Pruritus generalised | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Rash | 2/3 (66.7%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 5/17 (29.4%) | 1/7 (14.3%) | 13/17 (76.5%) | 33/163 (20.2%) | 4/56 (7.1%) | 3/22 (13.6%) | ||||||||||||
| Rash pruritic | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Scab | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Skin fissures | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Skin lesion | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Skin ulcer | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 1/17 (5.9%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Urticaria | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 2/56 (3.6%) | 0/22 (0%) | ||||||||||||
| Angioedema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Blister | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Decubitus ulcer | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Dermatitis acneiform | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Ecchymosis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 1/22 (4.5%) | ||||||||||||
| Exfoliative rash | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hyperkeratosis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Livedo reticularis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Night sweats | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Onychoclasis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Rash erythematous | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Rash papular | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Skin disorder | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Skin hyperpigmentation | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Subcutaneous emphysema | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Social circumstances | ||||||||||||||||||||||||
| Denture wearer | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Surgical and medical procedures | ||||||||||||||||||||||||
| Tooth extraction | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Tooth repair | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Vascular disorders | ||||||||||||||||||||||||
| Flushing | 0/3 (0%) | 1/2 (50%) | 0/4 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 3/17 (17.6%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Hot flush | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 1/17 (5.9%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypertension | 1/3 (33.3%) | 0/2 (0%) | 1/4 (25%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 1/17 (5.9%) | 5/163 (3.1%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypotension | 0/3 (0%) | 0/2 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/17 (5.9%) | 0/7 (0%) | 3/17 (17.6%) | 11/163 (6.7%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Orthostatic hypotension | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Pallor | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 1/17 (5.9%) | 2/163 (1.2%) | 1/56 (1.8%) | 0/22 (0%) | ||||||||||||
| Peripheral coldness | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 1/7 (14.3%) | 0/17 (0%) | 0/163 (0%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Thrombosis | 1/3 (33.3%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Deep vein thrombosis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Haematoma | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Hypovolaemic shock | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Ischaemia | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 1/163 (0.6%) | 0/56 (0%) | 0/22 (0%) | ||||||||||||
| Phlebitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 2/163 (1.2%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
| Thrombophlebitis | 0/3 (0%) | 0/2 (0%) | 0/4 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/17 (0%) | 0/7 (0%) | 0/17 (0%) | 0/163 (0%) | 1/56 (1.8%) | 1/22 (4.5%) | ||||||||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
Results Point of Contact
| Name/Title | Pfizer ClinicalTrials.gov Call Center |
|---|---|
| Organization | Pfizer, Inc. |
| Phone | 1-800-718-1021 |
| ClinicalTrials.gov_Inquiries@pfizer.com |
Responsible Party:
Pfizer
ClinicalTrials.gov Identifier:
NCT00147537
Other Study ID Numbers:
- A4021002
First Posted:
Sep 7, 2005
Last Update Posted:
Oct 30, 2013
Last Verified:
Oct 1, 2013