A Study To Assess The Safety Of PF-06342674 In Adults With Type 1 Diabetes
Sponsor
Pfizer (Industry)
Overall Status
Completed
CT.gov ID
NCT02038764
Collaborator
(none)
37
21
2
27.3
1.8
0.1
Study Details
Study Description
Brief Summary
The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics and immunogenicity of multiple doses of PF-06342674. Several dose levels will be evaluated.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
37 participants
Allocation:
Randomized
Masking:
Double (Participant, Investigator)
Primary Purpose:
Basic Science
Official Title:
A Phase 1 Study To Evaluate The Safety, Tolerability, Immunogenicity, Pharmacokinetics And Pharmacodynamics Of Multiple Ascending Doses Of Pf-06342674 (rn168) In Adults With Type 1 Diabetes
Actual Study Start Date
:
Jun 4, 2014
Actual Primary Completion Date
:
Sep 13, 2016
Actual Study Completion Date
:
Sep 13, 2016
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Placebo Comparator: Placebo Placebo |
Drug: Placebo
Placebo
|
| Experimental: PF-06342674
|
Biological: PF-06342674 Dose A
Multiple SC Doses
Biological: PF-06342674 Dose B
Multiple SC Doses
Biological: PF-06342674 Dose C
Multiple SC Doses
Biological: PF-06342674 Dose D
Multiple SC Doses
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) [Day 1 through Day 127]
Number of participants with dose limiting or intolerable treatment related adverse events (AEs) was reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage.
- Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) [Day 1 through Day 127]
Number of participants with all-causality treatment emergent adverse events were reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. TEAEs included both serious and non-serious AE
- Number of Participants With Treatment-Related TEAEs [Day 1 through Day 127]
Number of participants with treatment-related TEAEs were reported. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug.
- Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade [Day 1 through Day 127]
TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.
- Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events [Day 1 through Day 127]
Number of participants with all-causality treatment-emergent hypoglycemic adverse events was reported. Any blood glucose values less than(<)55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia.
- Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade [Day 1 through Day 127]
Any blood glucose values <55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE.
- Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) [Day 1 through Day 127]
The following laboratory test parameters were evaluated in this study: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),coagulation (partial thromboplastin time, prothrombin, and prothrombin international ratio), liver function(total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose, glycosylated, and hemoglobin), and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, urobilinogen, qualitative bilirubin, nitrites, leukocyte, esterase and microscopy).
- Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) [Day 1 through Day 127]
Number of participants with vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: SBP <90 millimeter of mercury(mmHg); Criterion B: DBP <50 mmHg; Criterion C: pulse rate < 40 beats per minute(BPM); Criterion D: pulse rate >120 BPM
- Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) [Day 1 through Day 127]
The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in systolic BP >= 30 mmHg; Criterion B: maximum decrease from baseline in diastolic BP >=20 mmHg
- Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) [Day 1 through Day 127]
The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in systolic BP >= 30 mmHg; Criterion B: maximum increase from baseline in diastolic BP >= 20 mmHg
- Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) [Day 1 through Day 127]
The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) >=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) >=200 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-<480 msec; Criterion D: maximum QTcF interval 480-<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) >=500 msec
- Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) [Day 1 through Day 127]
Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg >= 25/50%; Criterion C: maximum QTcF interval increase from baseline 30<=change<60 msec; Criterion D: maximum QTcF interval increase from baseline change >=60 msec.
- Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit [Day 1, Day 15, Day 29, Day 57, Day 85, and Day127 and follow-up visits]
Number of participants with serum anti-PF-06342674 antibody response to the intramuscular tetanus vaccine was reported. Positive Anti-PF-06342674 Antibody response is defined as anti-tetanus toxoid immunoglobulin G (IgG) titer value >=100
Secondary Outcome Measures
- Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 [0,1,4 hours post-dose on Day 1 and Day 71]
Area under the concentration-time profile from time 0 to time tau (τ), the dosing interval, where tau = 168 hours for once a week dosing; tau = 336 hours for once every 2 weeks dosing. On Day 1, 3 participants in cohort 1 had reportable AUCtau values. On Day 71, 6 participants in cohort 1 and 2 participants in cohort 4 had reportable AUCtau values
- Apparent Oral Clearance (CL/F) on Day 71 [0,1,4 hours post-dose on Day 71]
Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. On Day 71, 6 participants in cohort 1 had reportable CL/F values
- Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 [0, 1, 4 hours post-dose on Day 1 and Day 71]
Maximum serum concentration was observed directly from data on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Cmax values
- Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 [0, 1, 4 hours post-dose on Day 1 and Day 71]
Time to reach maximum observed plasma concentration was observed directly from data as time of first occurrence on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Tmax values
- Plasma Decay Half-Life (t1/2) on Day 71 [0, 1, 4 hours post-dose on Day 71]
Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. On Day 71, 2 participants in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable values for t1/2
- Apparent Volume of Distribution (Vz/F) on Day 71 [0, 1, 4 hours post-dose on Day 71]
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. On Day 71, 1 participant in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable Vz/F values
- Accumulation Ratio (Rac) on Day 71 [0, 1, 4, hours post-dose on Day 71]
Accumulation ratio was calculated from AUCinf at last dose/AUCinf at first dose, where AUCinf is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). On Day 71, 3 participants in cohort 1 had reportable Rac values.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Women and men age 18 and older.
-
Diagnosis of type 1 diabetes within 2 years of randomization.
-
Peak stimulated C-peptide levels ≥ 0.15 ng/mL.
Exclusion Criteria:
-
Anticipated ongoing use of diabetes medications other than insulin.
-
Evidence or history of diabetic complications with significant end-organ damage.
-
Episode of severe hypoglycemia within 60 days of randomization.
-
Multiple hospitalizations for diabetic ketoacidosis.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | VA San Diego Healthcare System (Drug Shipment) | San Diego | California | United States | 92161 |
| 2 | Veterans Administration San Diego Healthcare System | San Diego | California | United States | 92161 |
| 3 | University of California, San Francisco | San Francisco | California | United States | 94143 |
| 4 | Barbara Davis Center | Aurora | Colorado | United States | 80045 |
| 5 | Yale School of Medicine | New Haven | Connecticut | United States | 06510 |
| 6 | Yale New Haven Hospital - Investigational Drug Services | New Haven | Connecticut | United States | 06511 |
| 7 | Yale University School of Medicine | New Haven | Connecticut | United States | 06519 |
| 8 | Atlanta Diabetes Associates | Atlanta | Georgia | United States | 30318 |
| 9 | Duchossois Center for Advanced Medicine | Chicago | Illinois | United States | 60637 |
| 10 | The University of Chicago Medical Center | Chicago | Illinois | United States | 60637 |
| 11 | University of Chicago Clinical Resource Center | Chicago | Illinois | United States | 60637 |
| 12 | University of Chicago Medical Center | Chicago | Illinois | United States | 60637 |
| 13 | Umass Memorial Medical Center | Worcester | Massachusetts | United States | 01655 |
| 14 | University of Massachusetts Medical School | Worcester | Massachusetts | United States | 01655 |
| 15 | University Of Minnesota Fairview Pharmacy Services | Minneapolis | Minnesota | United States | 55454 |
| 16 | University Of Minnesota Medical School | Minneapolis | Minnesota | United States | 55455 |
| 17 | Barnes- Jewish HOSP Att: Kathryn Vehe | Saint Louis | Missouri | United States | 63110 |
| 18 | Washington University - Center for Advanced Medicine | Saint Louis | Missouri | United States | 63110 |
| 19 | Washington University | Saint Louis | Missouri | United States | 63110 |
| 20 | Duke Clinical Research Unit | Durham | North Carolina | United States | 27710 |
| 21 | Duke University Health Systems (DUHS) Investigational Drug Services | Durham | North Carolina | United States | 27710 |
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:
NCT02038764
Other Study ID Numbers:
- B4351003
First Posted:
Jan 17, 2014
Last Update Posted:
Aug 3, 2018
Last Verified:
Oct 1, 2017
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Pfizer
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | A total of 37 participants were assigned to study treatment (placebo: 7 subjects; PF-06342674: 30 subjects) |
| Arm/Group Title | Placebo | PF-06342674 1 mg/kg | PF-06342674 3 mg/kg | PF-06342674 6 mg/kg | PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Period Title: Overall Study | |||||
| STARTED | 7 | 8 | 9 | 5 | 8 |
| COMPLETED | 6 | 7 | 7 | 5 | 7 |
| NOT COMPLETED | 1 | 1 | 2 | 0 | 1 |
Baseline Characteristics
| Arm/Group Title | Placebo | PF-06342674 1 mg/kg | PF-06342674 3 mg/kg | PF-06342674 6 mg/kg | PF-06342674 8 mg/kg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Total of all reporting groups |
| Overall Participants | 7 | 8 | 9 | 5 | 8 | 37 |
| Age (years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [years] |
33.9
(11.1)
|
25.6
(8.5)
|
37.8
(15.8)
|
29
(12.3)
|
30.8
(7.7)
|
31.7
(11.8)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
2
28.6%
|
3
37.5%
|
6
66.7%
|
0
0%
|
4
50%
|
15
40.5%
|
| Male |
5
71.4%
|
5
62.5%
|
3
33.3%
|
5
100%
|
4
50%
|
22
59.5%
|
Outcome Measures
| Title | Number of Participants With Dose Limiting or Intolerable Treatment Related Adverse Events (AEs) |
|---|---|
| Description | Number of participants with dose limiting or intolerable treatment related adverse events (AEs) was reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event need not necessarily have a causal relationship with the treatment or usage. |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Number [participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
| Title | Number of Participants With All-Causality Treatment Emergent Adverse Events(TEAEs) |
|---|---|
| Description | Number of participants with all-causality treatment emergent adverse events were reported. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. TEAEs included both serious and non-serious AE |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Number [participants] |
7
100%
|
8
100%
|
7
77.8%
|
5
100%
|
6
75%
|
| Title | Number of Participants With Treatment-Related TEAEs |
|---|---|
| Description | Number of participants with treatment-related TEAEs were reported. Treatment-related AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An AE was any untoward medical occurrence in a clinical investigation subject administered a product or medical device; the event needed not necessarily have a causal relationship with the treatment or usage. TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Number [participants] |
5
71.4%
|
6
75%
|
6
66.7%
|
4
80%
|
5
62.5%
|
| Title | Number of Participants With All-Causality TEAEs Listed by Common Terminology Criteria for Adverse Events (CTCAE) Grade |
|---|---|
| Description | TEAEs were those AEs with initial onset or increasing in severity after the first dose of study drug. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE. |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Grade 1 |
3
42.9%
|
2
25%
|
1
11.1%
|
3
60%
|
1
12.5%
|
| Grade 2 |
2
28.6%
|
6
75%
|
4
44.4%
|
0
0%
|
4
50%
|
| Grade 3 |
2
28.6%
|
0
0%
|
2
22.2%
|
2
40%
|
1
12.5%
|
| Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events |
|---|---|
| Description | Number of participants with all-causality treatment-emergent hypoglycemic adverse events was reported. Any blood glucose values less than(<)55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia. |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Number [participants] |
4
57.1%
|
4
50%
|
5
55.6%
|
1
20%
|
3
37.5%
|
| Title | Number of Participants With All-Causality Treatment-Emergent Hypoglycemic Adverse Events Listed by CTCAE Grade |
|---|---|
| Description | Any blood glucose values <55 mg/dL with or without symptoms was reported as adverse events of hypoglycemia. CTCAE version 4.03 was used to grade the severity of TEAEs. Grade 1 referred to mild AEs; Grade 2 referred to moderate AEs; Grade 3 referred to severe AEs; Grade 4 referred to AEs with life-threatening consequences, and urgent intervention was needed to manage them; Grade 5 referred to death related to AE. |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Grade 1 |
1
14.3%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
| Grade 2 |
1
14.3%
|
4
50%
|
3
33.3%
|
0
0%
|
2
25%
|
| Grade 3 |
2
28.6%
|
0
0%
|
1
11.1%
|
1
20%
|
1
12.5%
|
| Grade 4 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Grade 5 |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Laboratory Test Abnormalities (Without Regard to Baseline Abnormality) |
|---|---|
| Description | The following laboratory test parameters were evaluated in this study: hematology (hemoglobin, hematocrit, red blood cell count, platelet count, white blood cell count, absolute total neutrophils, absolute eosinophils, absolute basophils, absolute monocytes, and absolute lymphocytes),coagulation (partial thromboplastin time, prothrombin, and prothrombin international ratio), liver function(total bilirubin, direct bilirubin, indirect bilirubin, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, and albumin), renal function (blood urea nitrogen, creatinine, and uric acid), electrolytes (sodium, potassium, chloride, calcium, and venous bicarbonate), clinical chemistry(glucose, glycosylated, and hemoglobin), and urinalysis (pH, qualitative glucose, qualitative protein, qualitative blood, urobilinogen, qualitative bilirubin, nitrites, leukocyte, esterase and microscopy). |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Number [participants] |
7
100%
|
7
87.5%
|
8
88.9%
|
5
100%
|
7
87.5%
|
| Title | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Absolute Values) |
|---|---|
| Description | Number of participants with vital signs data of absolute values meeting criteria of potential clinical concern. Absolute values were analyzed for systolic blood pressure (SBP), diastolic blood pressure (DBP), and pulse rate. Number of participants with vital signs data meeting the following criteria was reported: Criterion A: SBP <90 millimeter of mercury(mmHg); Criterion B: DBP <50 mmHg; Criterion C: pulse rate < 40 beats per minute(BPM); Criterion D: pulse rate >120 BPM |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Criterion A |
0
0%
|
0
0%
|
1
11.1%
|
0
0%
|
0
0%
|
| Criterion B |
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Criterion C |
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Criterion D |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Decreases From Baseline) |
|---|---|
| Description | The number of participants with vital signs data of maximum decrease from baseline meeting the following criteria was reported: Criterion A: maximum decrease from baseline in systolic BP >= 30 mmHg; Criterion B: maximum decrease from baseline in diastolic BP >=20 mmHg |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Criterion A |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Criterion B |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
12.5%
|
| Title | Number of Participants With Vital Signs That Met the Criteria for Potential Clinical Concern(Increases From Baseline) |
|---|---|
| Description | The number of participants with vital signs data of maximum increase from baseline meeting the following criteria was reported: Criterion A: maximum increase from baseline in systolic BP >= 30 mmHg; Criterion B: maximum increase from baseline in diastolic BP >= 20 mmHg |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Criterion A |
0
0%
|
0
0%
|
0
0%
|
1
20%
|
0
0%
|
| Criterion B |
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Absolute Value) |
|---|---|
| Description | The number of participants with ECG absolute values meeting the following criteria was reported: Criterion A: maximum PR interval (time from the beginning of P wave to the start of QRS complex, corresponding to the end of atrial depolarization and onset of ventricular depolarization) >=300 msec; Criterion B: maximum QRS complex(time from Q wave to the end of S wave, corresponding to ventricle depolarization) >=200 msec; Criterion C: maximum QTcF interval (time from the beginning of Q wave to the end of T wave corresponding to electrical systole, corrected for heart rate using Fridericia's formula) 450-<480 msec; Criterion D: maximum QTcF interval 480-<500 msec; Criterion E: maximum QTcF interval (Fridericia's correction) >=500 msec |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Criterion A |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Criterion B |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Criterion C |
1
14.3%
|
0
0%
|
3
33.3%
|
1
20%
|
0
0%
|
| Criterion D |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Criterion E |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Electrocardiogram(ECG) Data That Met the Criteria for Potential Clinical Concern(Increases From Baseline) |
|---|---|
| Description | Number of participants with ECG meeting the following criteria was reported: Criterion A: maximum PR interval increase from baseline percentage change (PctChg)>= 25/50%; Criterion B: maximum QRS complex increase from baseline PctChg >= 25/50%; Criterion C: maximum QTcF interval increase from baseline 30<=change<60 msec; Criterion D: maximum QTcF interval increase from baseline change >=60 msec. |
| Time Frame | Day 1 through Day 127 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Criterion A |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Criterion B |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Criterion C |
1
14.3%
|
0
0%
|
2
22.2%
|
0
0%
|
1
12.5%
|
| Criterion D |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Title | Number of Participants With Serum Anti-PF-06342674 Antibody Response Listed by Visit |
|---|---|
| Description | Number of participants with serum anti-PF-06342674 antibody response to the intramuscular tetanus vaccine was reported. Positive Anti-PF-06342674 Antibody response is defined as anti-tetanus toxoid immunoglobulin G (IgG) titer value >=100 |
| Time Frame | Day 1, Day 15, Day 29, Day 57, Day 85, and Day127 and follow-up visits |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of study medication. |
| Arm/Group Title | Placebo | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 7 | 8 | 9 | 5 | 8 |
| Day 1 Negative |
2
28.6%
|
8
100%
|
9
100%
|
5
100%
|
8
100%
|
| Day 1 Positive |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Day 15 Negative |
2
28.6%
|
6
75%
|
6
66.7%
|
5
100%
|
8
100%
|
| Day 15 Positive |
0
0%
|
2
25%
|
2
22.2%
|
0
0%
|
0
0%
|
| Day 29 Negative |
2
28.6%
|
4
50%
|
6
66.7%
|
5
100%
|
8
100%
|
| Day 29 Positive |
0
0%
|
4
50%
|
2
22.2%
|
0
0%
|
0
0%
|
| Day 57 Negative |
1
14.3%
|
4
50%
|
4
44.4%
|
3
60%
|
7
87.5%
|
| Day 57 Positive |
0
0%
|
4
50%
|
4
44.4%
|
2
40%
|
1
12.5%
|
| Day 85 Negative |
1
14.3%
|
3
37.5%
|
4
44.4%
|
1
20%
|
4
50%
|
| Day 85 Positive |
0
0%
|
5
62.5%
|
3
33.3%
|
4
80%
|
4
50%
|
| Day 127 Negative |
1
14.3%
|
2
25%
|
5
55.6%
|
0
0%
|
2
25%
|
| Day 127 Positive |
0
0%
|
6
75%
|
2
22.2%
|
5
100%
|
6
75%
|
| Follow-up1 Negative |
0
0%
|
1
12.5%
|
0
0%
|
0
0%
|
2
25%
|
| Follow-up1 Positive |
0
0%
|
4
50%
|
3
33.3%
|
5
100%
|
5
62.5%
|
| Follow-up2 Negative |
0
0%
|
3
37.5%
|
1
11.1%
|
0
0%
|
3
37.5%
|
| Follow-up2 Positive |
0
0%
|
1
12.5%
|
1
11.1%
|
5
100%
|
1
12.5%
|
| Follow-up3 Negative |
0
0%
|
1
12.5%
|
0
0%
|
4
80%
|
0
0%
|
| Follow-up3 Positive |
0
0%
|
1
12.5%
|
1
11.1%
|
1
20%
|
1
12.5%
|
| Title | Area Under Concentration-Time Curve From Time Zero to Time Tau(AUCtau) on Day 1 and Day 71 |
|---|---|
| Description | Area under the concentration-time profile from time 0 to time tau (τ), the dosing interval, where tau = 168 hours for once a week dosing; tau = 336 hours for once every 2 weeks dosing. On Day 1, 3 participants in cohort 1 had reportable AUCtau values. On Day 71, 6 participants in cohort 1 and 2 participants in cohort 4 had reportable AUCtau values |
| Time Frame | 0,1,4 hours post-dose on Day 1 and Day 71 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. On Day 1, 3 participants in cohort 1 had reportable AUCtau values. On Day 71, 6 participants in cohort 1 and 2 participants in cohort 4 had reportable AUCtau values |
| Arm/Group Title | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 8 | 8 | 5 | 8 |
| Day 1 |
384900
(43)
|
1323000
(43)
|
2570000
(31)
|
5805000
(28)
|
| Day 71 |
426700
(58)
|
2029000
(29)
|
NA
(NA)
|
7869000
(42)
|
| Title | Apparent Oral Clearance (CL/F) on Day 71 |
|---|---|
| Description | Clearance of a drug is a measure of the rate at which a drug is metabolized or eliminated by normal biological processes. Clearance obtained after oral dose (apparent oral clearance) is influenced by the fraction of the dose absorbed. Clearance was estimated from population pharmacokinetic (PK) modeling. Drug clearance is a quantitative measure of the rate at which a drug substance is removed from the blood. On Day 71, 6 participants in cohort 1 had reportable CL/F values |
| Time Frame | 0,1,4 hours post-dose on Day 71 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. Day 71, 6 participants in cohort 1 had reportable CL/F values |
| Arm/Group Title | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 8 | 8 | 2 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [mL/hr/kg] |
2.340
(58)
|
1.477
(29)
|
NA
(NA)
|
1.017
(42)
|
| Title | Maximum Observed Plasma Concentration (Cmax) on Day 1 and Day 71 |
|---|---|
| Description | Maximum serum concentration was observed directly from data on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Cmax values |
| Time Frame | 0, 1, 4 hours post-dose on Day 1 and Day 71 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants treated who had at least 1 concentration value. On Day 71, 2 participants in cohort 4 had reportable Cmax values |
| Arm/Group Title | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 8 | 8 | 5 | 8 |
| Day 1 |
2114
(83)
|
8512
(42)
|
20890
(29)
|
31610
(27)
|
| Day 71 |
2612
(89)
|
10600
(22)
|
NA
(NA)
|
39870
(34)
|
| Title | Time to Reach Maximum Observed Plasma Concentration (Tmax) on Day 1 and Day 71 |
|---|---|
| Description | Time to reach maximum observed plasma concentration was observed directly from data as time of first occurrence on Day 1 and Day 71. On Day 71, 2 participants in cohort 4 had reportable Tmax values |
| Time Frame | 0, 1, 4 hours post-dose on Day 1 and Day 71 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed.On Day 71, 2 participants in cohort 4 had reportable Tmax values |
| Arm/Group Title | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 8 | 8 | 5 | 8 |
| Day 1 |
48.8
(83)
|
48.9
(42)
|
48.1
(29)
|
51.8
(27)
|
| Day 71 |
48.9
(89)
|
60.2
(22)
|
NA
(NA)
|
86.3
(34)
|
| Title | Plasma Decay Half-Life (t1/2) on Day 71 |
|---|---|
| Description | Plasma decay half-life is the time measured for the plasma concentration to decrease by one half. On Day 71, 2 participants in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable values for t1/2 |
| Time Frame | 0, 1, 4 hours post-dose on Day 71 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. On Day 71, 2 participants in cohort 1 , 5 participants in cohort 2, and 7 participants in cohort 3 had reportable values for t1/2 |
| Arm/Group Title | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 8 | 8 | 2 | 8 |
| Mean (Standard Deviation) [hr] |
NA
(NA)
|
64.62
(7.34)
|
NA
(NA)
|
85.54
(23.54)
|
| Title | Apparent Volume of Distribution (Vz/F) on Day 71 |
|---|---|
| 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. On Day 71, 1 participant in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable Vz/F values |
| Time Frame | 0, 1, 4 hours post-dose on Day 71 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. On Day 71, 1 participant in cohort 1, 5 participants in cohort 2, and 7 participants in cohort 3 had reportable Vz/F values |
| Arm/Group Title | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 8 | 8 | 2 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [mL/kg] |
NA
(NA)
|
141.2
(18)
|
NA
(NA)
|
129.5
(18)
|
| Title | Accumulation Ratio (Rac) on Day 71 |
|---|---|
| Description | Accumulation ratio was calculated from AUCinf at last dose/AUCinf at first dose, where AUCinf is defined as area under the plasma concentration versus time curve (AUC) from time zero (pre-dose) to extrapolated infinite time (0-inf). It is obtained from AUC (0-t) plus AUC (t-inf). On Day 71, 3 participants in cohort 1 had reportable Rac values. |
| Time Frame | 0, 1, 4, hours post-dose on Day 71 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants randomized and treated who had at least 1 of the PK parameters of interest were analyzed. On Day 71, 3 participants in cohort 1 had reportable Rac values. |
| Arm/Group Title | Cohort 1 PF-06342674 1 mg/kg | Cohort 2 PF-06342674 3 mg/kg | Cohort 4 PF-06342674 6 mg/kg | Cohort 3 PF-06342674 8 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. |
| Measure Participants | 8 | 8 | 2 | 8 |
| Geometric Mean (Geometric Coefficient of Variation) [Ratio] |
1.115
(48)
|
1.532
(28)
|
NA
(NA)
|
1.355
(19)
|
Adverse Events
| Time Frame | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||
| Arm/Group Title | Placebo | PF-06342674 1 mg/kg | PF-06342674 3 mg/kg | PF-06342674 6 mg/kg | PF-06342674 8 mg/kg | |||||
| Arm/Group Description | Participants were randomly assigned to placebo in a 2/8 ratio in Cohorts 1 through 3 and a 1/4 ratio in Cohort 4. The treatment was given as a subcutaneous injection(s) | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | Participants received their dose as a subcutaneous injection(s) once a week (q1w) up to 12 doses. | Participants received their dose as a subcutaneous injection(s) once every two weeks (q2w) up to 6 doses. | |||||
All Cause Mortality |
||||||||||
| Placebo | PF-06342674 1 mg/kg | PF-06342674 3 mg/kg | PF-06342674 6 mg/kg | PF-06342674 8 mg/kg | ||||||
| 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) | |||||
Serious Adverse Events |
||||||||||
| Placebo | PF-06342674 1 mg/kg | PF-06342674 3 mg/kg | PF-06342674 6 mg/kg | PF-06342674 8 mg/kg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
| Cardiac disorders | ||||||||||
| Atrial fibrillation | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
Other (Not Including Serious) Adverse Events |
||||||||||
| Placebo | PF-06342674 1 mg/kg | PF-06342674 3 mg/kg | PF-06342674 6 mg/kg | PF-06342674 8 mg/kg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 5/7 (71.4%) | 6/8 (75%) | 6/9 (66.7%) | 4/5 (80%) | 5/8 (62.5%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Lymphadenopathy | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 1/5 (20%) | 1/8 (12.5%) | |||||
| Splenomegaly | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Cardiac disorders | ||||||||||
| Palpitations | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Ear and labyrinth disorders | ||||||||||
| Vertigo | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 1/8 (12.5%) | |||||
| Eye disorders | ||||||||||
| Eye irritation | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Eye oedema | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Vision blurred | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 1/8 (12.5%) | |||||
| Gastrointestinal disorders | ||||||||||
| Abdominal distension | 1/7 (14.3%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
| Abdominal pain | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Diarrhoea | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 1/8 (12.5%) | |||||
| Dry mouth | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Lip dry | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Nausea | 0/7 (0%) | 1/8 (12.5%) | 2/9 (22.2%) | 1/5 (20%) | 0/8 (0%) | |||||
| Vomiting | 1/7 (14.3%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
| General disorders | ||||||||||
| Fatigue | 2/7 (28.6%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 1/8 (12.5%) | |||||
| Injection site bruising | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 1/5 (20%) | 0/8 (0%) | |||||
| Injection site erythema | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 1/8 (12.5%) | |||||
| Injection site induration | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 1/8 (12.5%) | |||||
| Injection site pain | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 1/8 (12.5%) | |||||
| Injection site pruritus | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 1/8 (12.5%) | |||||
| Malaise | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 1/8 (12.5%) | |||||
| Pain | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Peripheral swelling | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Infections and infestations | ||||||||||
| Epstein-Barr virus infection | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Infectious mononucleosis | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Nasopharyngitis | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 2/8 (25%) | |||||
| Sinusitis | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Upper respiratory tract infection | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Viral infection | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Injury, poisoning and procedural complications | ||||||||||
| Contusion | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Investigations | ||||||||||
| Aspartate aminotransferase increased | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| CD4 lymphocytes decreased | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Electrocardiogram QT prolonged | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Epstein-Barr virus antibody positive | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Lymphocyte count decreased | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 2/5 (40%) | 1/8 (12.5%) | |||||
| Neutrophil count decreased | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| White blood cell count decreased | 1/7 (14.3%) | 1/8 (12.5%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Metabolism and nutrition disorders | ||||||||||
| Hypoglycaemia | 2/7 (28.6%) | 1/8 (12.5%) | 1/9 (11.1%) | 1/5 (20%) | 0/8 (0%) | |||||
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
| Myalgia | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Nervous system disorders | ||||||||||
| Dizziness | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 1/8 (12.5%) | |||||
| Headache | 0/7 (0%) | 2/8 (25%) | 2/9 (22.2%) | 0/5 (0%) | 3/8 (37.5%) | |||||
| Lethargy | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 1/5 (20%) | 0/8 (0%) | |||||
| Presyncope | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 1/5 (20%) | 1/8 (12.5%) | |||||
| Dyspnoea exertional | 0/7 (0%) | 0/8 (0%) | 0/9 (0%) | 1/5 (20%) | 0/8 (0%) | |||||
| Haemoptysis | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Nasal congestion | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
| Oropharyngeal pain | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 1/5 (20%) | 1/8 (12.5%) | |||||
| Productive cough | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Rhinorrhoea | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
| Tonsillar hypertrophy | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Skin and subcutaneous tissue disorders | ||||||||||
| Erythema | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
| Hyperhidrosis | 1/7 (14.3%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Rash | 1/7 (14.3%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Skin irritation | 1/7 (14.3%) | 0/8 (0%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Urticaria | 0/7 (0%) | 1/8 (12.5%) | 0/9 (0%) | 0/5 (0%) | 0/8 (0%) | |||||
| Vascular disorders | ||||||||||
| Pallor | 0/7 (0%) | 0/8 (0%) | 1/9 (11.1%) | 0/5 (0%) | 0/8 (0%) | |||||
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:
NCT02038764
Other Study ID Numbers:
- B4351003
First Posted:
Jan 17, 2014
Last Update Posted:
Aug 3, 2018
Last Verified:
Oct 1, 2017