Oprozomib and Dexamethasone,in Combination With Lenalidomide or Oral Cyclophosphamide to Treat Newly Diagnosed Multiple Myeloma
Sponsor
Amgen (Industry)
Overall Status
Terminated
CT.gov ID
NCT01881789
Collaborator
(none)
22
14
6
70.8
1.6
0
Study Details
Study Description
Brief Summary
The primary objectives of this study included the following:
Phase 1b:
-
To establish the maximum tolerated dose (MTD) of oprozomib given in combination with lenalidomide and dexamethasone (ORd) or with cyclophosphamide and dexamethasone (OCyd)
-
To evaluate the safety and tolerability of oprozomib and dexamethasone administered in combination with lenalidomide or oral cyclophosphamide
Phase 2:
-
To estimate the antitumor activity of each combination regimen, as measured by overall response rate (ORR) and complete response rate (CRR)
-
To evaluate the safety and tolerability of each combination regimens, as assessed by the type, incidence, severity and seriousness of adverse events, and abnormalities in selected laboratory analytes
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1/Phase 2 |
Detailed Description
Phase 1b used a standard 3 + 3 dose-escalation scheme to determine the MTD. For each combination regimen, oprozomib doses were to be escalated in sequential cohorts of 3 participants with expansion to up to 6 participants if a dose-limiting toxicity (DLT) was observed in 1 of the first 3 participants. The doses of lenalidomide, cyclophosphamide, and dexamethasone were to remain fixed in all dose cohorts.
The phase 2 portion of the study was to include up to 35 additional participants in each of the 2 combination regimens, treated at the recommended phase 2 dose (RP2D) of oprozomib that was identified during the phase 1b portion of the study in order to better characterize safety and tolerability, and antimyeloma activity.
This study was stopped by sponsor decision during the dose escalation in phase 1b prior to initiation of phase 2.
Study Design
Study Type:
Interventional
Actual Enrollment
:
22 participants
Allocation:
Non-Randomized
Intervention Model:
Sequential Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Phase 1b/2, Multicenter, Open-label Study of Oprozomib and Dexamethasone, in Combination With Lenalidomide or Oral Cyclophosphamide in Patients With Newly Diagnosed Multiple Myeloma
Actual Study Start Date
:
Oct 28, 2013
Actual Primary Completion Date
:
Sep 23, 2019
Actual Study Completion Date
:
Sep 23, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. |
Drug: Oprozomib
Extended release (ER) tablets administered orally
Other Names:
Drug: Lenalidomide
Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.
Other Names:
Drug: Dexamethasone
Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants > 75 years of age, at the discretion of the investigator.
|
| Experimental: Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. |
Drug: Oprozomib
Extended release (ER) tablets administered orally
Other Names:
Drug: Lenalidomide
Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.
Other Names:
Drug: Dexamethasone
Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants > 75 years of age, at the discretion of the investigator.
|
| Experimental: Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. |
Drug: Oprozomib
Extended release (ER) tablets administered orally
Other Names:
Drug: Lenalidomide
Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.
Other Names:
Drug: Dexamethasone
Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants > 75 years of age, at the discretion of the investigator.
|
| Experimental: Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. |
Drug: Oprozomib
Extended release (ER) tablets administered orally
Other Names:
Drug: Lenalidomide
Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.
Other Names:
Drug: Dexamethasone
Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants > 75 years of age, at the discretion of the investigator.
|
| Experimental: Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. |
Drug: Oprozomib
Extended release (ER) tablets administered orally
Other Names:
Drug: Lenalidomide
Administered orally at a dose of 25 mg on days 1 through 21 of each 28-day cycle for a maximum of 24 cycles.
Other Names:
Drug: Dexamethasone
Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants > 75 years of age, at the discretion of the investigator.
|
| Experimental: Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. |
Drug: Oprozomib
Extended release (ER) tablets administered orally
Other Names:
Drug: Dexamethasone
Administered at 20 mg, orally, on days 1, 2, 8, 9, 15, 16, 22, and 23 of each 28-day cycle. After the first cycle the dose may be decreased to 10 mg/day in participants > 75 years of age, at the discretion of the investigator.
Drug: Cyclophosphamide
Administered orally at 300 mg/m² (up to a maximum of 600 mg) on days 1, 8, and 15 of each 28-day cycle for a maximum of 8 cycles of therapy (approximately 8 months).
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Dose-Limiting Toxicities (DLTs) [Cycle 1, 28 days]
DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. A DLT is defined as any of the following treatment-related events: Any ≥ Grade 3 nonhematologic toxicity with the following conditions: ≥ Grade 3 nausea, vomiting, diarrhea, or constipation only if for > 7 days despite optimal supportive care Asymptomatic Grade 3 hypophosphatemia, Grade 3 hyperglycemia or toxicity solely due to dexamethasone, ≥ Grade 3 rash attributed to lenalidomide, and Grade 3 fatigue for < 14 days were not considered DLTs Grade 4 neutropenia: absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting ≥ 7 days, despite myeloid growth factor support Febrile neutropenia Grade 4 thrombocytopenia for ≥ 7 days or < 7 days with ≥ Grade 2 clinically significant bleeding or < 10,000 platelets requiring platelet transfusion, or Grade ≥ 3 with clinically significant bleeding or requiring platelet transfusion.
- Number of Participants With Treatment-emergent Adverse Events (AEs) [From first dose of any study treatment to 30 days after last dose; median duration of treatment was 29.1, 12.4, 11.3, 66.6, 7.8, and 46.4 weeks in each treatment group, respectively.]
Adverse events (AEs) were graded using NCI-CTCAE (version 4.03) and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. A serious AE is an event that met 1 or more of the following criteria: Death Life-threatening experience Required inpatient hospitalization or prolongation of an existing hospitalization Resulted in persistent or significant disability/incapacity A congenital anomaly birth defect in the offspring of an exposed female subject or offspring of a female partner of a male subject Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent an outcome listed above. Treatment-related AEs are those considered related to at least 1 study drug by the investigator.
Secondary Outcome Measures
- Plasma Oprozomib Concentration [Cycle 1 day 1 at 1 to 2.5 hours and 2.75 to 5 hours after end of infusion (EOI) and cycle 3 day 1 at predose and 1 to 2.5 hours and 2.75 to 5 hours after EOI.]
Plasma samples for oprozomib concentration assays were only collected for participants in the 5/14 dosing schedule groups. Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry.
- Overall Response Rate (ORR) [Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median duration of treatment at the analysis cutoff date of 18 July 2016 was 29.1, 12.4, 11.3, 66.6, 7.8 and 46.4 weeks in each group, respectively]
ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria. PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline. VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC. sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM).
- Duration of Response (DOR) [Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median time on follow-up at the analysis cut-off date of 18 July 2016 was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively.]
Duration of response was defined as the time from first evidence of partial response (PR) or better to confirmation of disease progression or death due to any cause. Median DOR was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment.
- Progression-Free Survival (PFS) [From first dose of study drug through the data cut-off date of 18 July 2016; median time on follow-up was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively]
Progression-free survival is defined as the time from the start of treatment to disease progression or death (due to any cause), whichever occurred first. Median PFS was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Key Inclusion Criteria:
-
Newly diagnosed, symptomatic multiple myeloma patients for whom treatment is indicated per the National Comprehensive Cancer Network (NCCN) guidelines, and for whom a hematopoietic stem cell transplant is not planned or scheduled during the study or are considered ineligible for hematopoietic stem cell transplant, with measurable disease
-
Creatinine clearance of ≥ 50 mL/min (measured or calculated using the Cockcroft and Gault formula)
Key Exclusion Criteria:
-
Any prior systemic antimyeloma therapy except oral steroids (dexamethasone up to a total dose of 160 mg or equivalent within 14 days prior to the first dose of study treatment). Use of topical or inhaled steroids is acceptable
-
Radiation therapy within 2 weeks prior to first dose
-
Major surgery within 3 weeks prior to first dose
-
Active infection requiring systemic antibiotics, antivirals, or antifungals within 2 weeks prior to first dose
-
Clinical significant gastrointestinal bleeding in the 6 months prior to Cycle 1 Day 1 (C1D1) first dose
-
Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of first dose
-
Other malignancy within the past 3 years except those considered cured by surgical resection including some cases of: with the exception of adequately treated basal or squamous cell carcinoma of the skin, squamous cell skin cancer, thyroid cancer, carcinoma in situ of the breast or cervix, carcinoma in situ of the breast, prostate cancer with Gleason Score 6 or less with stable prostate specific antigen levels, or cancer considered cured by surgical resection
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Clearview Cancer Institute | Huntsville | Alabama | United States | |
| 2 | Providence St. Joseph's Hospital | Burbank | California | United States | |
| 3 | David Geffen School of Medicine at UCLA | Los Angeles | California | United States | |
| 4 | Monterey Bay Oncology Corp DBA Pacific Cancer Care | Salinas | California | United States | |
| 5 | Colorado Blood Cancer Institute | Denver | Colorado | United States | |
| 6 | H. Lee Moffit Cancer Center & Research Institute | Tampa | Florida | United States | |
| 7 | University of Chicago Medical Center | Chicago | Illinois | United States | |
| 8 | Indiana University Health Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | United States | |
| 9 | Center for Cancer & Blood Disorders | Bethesda | Maryland | United States | |
| 10 | The University of North Carolina at Chapel Hill | Chapel Hill | North Carolina | United States | |
| 11 | Cleveland Clinic | Cleveland | Ohio | United States | |
| 12 | University of Texas M.D. Anderson Cancer Center | Houston | Texas | United States | |
| 13 | Fred Hutchinson Cancer Research Center | Seattle | Washington | United States | |
| 14 | Froedtert Hospital and the Medical College of Wisconsin | Milwaukee | Wisconsin | United States |
Sponsors and Collaborators
- Amgen
Investigators
- Study Director: MD, Amgen
Study Documents (Full-Text)
More Information
Additional Information:
Publications
None provided.Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01881789
Other Study ID Numbers:
- OPZ003
- 20130410
First Posted:
Jun 20, 2013
Last Update Posted:
Mar 25, 2021
Last Verified:
Feb 1, 2021
Keywords provided by Amgen
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | This study was conducted at 17 study centers in the United States. Twenty-two participants were enrolled, however one participant discontinued before being assigned to a treatment cohort. Enrollment was halted during dose-escalation and Phase 2 was not conducted. |
|---|---|
| Pre-assignment Detail | In the Phase 1b portion of the study participants were enrolled sequentially using a standard 3 + 3 dose escalation schema. The final planned analysis for efficacy was performed using a data cut-off date of 18 July 2016, at which time 3 participants remained on treatment. The final analysis of safety was conducted after all participants had discontinued treatment (23 September 2019). |
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. |
| Period Title: Overall Study | ||||||
| STARTED | 3 | 7 | 3 | 3 | 2 | 3 |
| COMPLETED | 0 | 0 | 0 | 0 | 0 | 0 |
| NOT COMPLETED | 3 | 7 | 3 | 3 | 2 | 3 |
Baseline Characteristics
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | Total |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. | Total of all reporting groups |
| Overall Participants | 3 | 7 | 3 | 3 | 2 | 3 | 21 |
| Age (years) [Mean (Standard Deviation) ] | |||||||
| Mean (Standard Deviation) [years] |
72.3
(6.1)
|
68.9
(8.7)
|
64.7
(2.5)
|
64.7
(11.0)
|
60.0
(5.7)
|
67.7
(4.2)
|
67.1
(7.4)
|
| Sex: Female, Male (Count of Participants) | |||||||
| Female |
0
0%
|
2
28.6%
|
2
66.7%
|
0
0%
|
2
100%
|
0
0%
|
6
28.6%
|
| Male |
3
100%
|
5
71.4%
|
1
33.3%
|
3
100%
|
0
0%
|
3
100%
|
15
71.4%
|
| Ethnicity (NIH/OMB) (Count of Participants) | |||||||
| Hispanic or Latino |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
4.8%
|
| Not Hispanic or Latino |
3
100%
|
6
85.7%
|
3
100%
|
3
100%
|
2
100%
|
3
100%
|
20
95.2%
|
| Unknown or Not Reported |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Race/Ethnicity, Customized (Count of Participants) | |||||||
| American Indian or Alaska Native |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
1
4.8%
|
| Asian |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Black |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
4.8%
|
| Native Hawaiian or Other Pacific Islander |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| White |
3
100%
|
5
71.4%
|
3
100%
|
2
66.7%
|
2
100%
|
3
100%
|
18
85.7%
|
| Other |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Not Reported |
0
0%
|
1
14.3%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
4.8%
|
| Eastern Cooperative Oncology Group (ECOG) Performance Status (Count of Participants) | |||||||
| Grade 0 (Fully active) |
1
33.3%
|
4
57.1%
|
3
100%
|
1
33.3%
|
1
50%
|
3
100%
|
13
61.9%
|
| Grade 1 (Restricted but ambulatory) |
2
66.7%
|
3
42.9%
|
0
0%
|
2
66.7%
|
1
50%
|
0
0%
|
8
38.1%
|
| Grade 2 (Ambulatory but unable to work) |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
Outcome Measures
| Title | Number of Participants With Dose-Limiting Toxicities (DLTs) |
|---|---|
| Description | DLTs were assessed according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03. A DLT is defined as any of the following treatment-related events: Any ≥ Grade 3 nonhematologic toxicity with the following conditions: ≥ Grade 3 nausea, vomiting, diarrhea, or constipation only if for > 7 days despite optimal supportive care Asymptomatic Grade 3 hypophosphatemia, Grade 3 hyperglycemia or toxicity solely due to dexamethasone, ≥ Grade 3 rash attributed to lenalidomide, and Grade 3 fatigue for < 14 days were not considered DLTs Grade 4 neutropenia: absolute neutrophil count (ANC) < 0.5 × 10^9/L lasting ≥ 7 days, despite myeloid growth factor support Febrile neutropenia Grade 4 thrombocytopenia for ≥ 7 days or < 7 days with ≥ Grade 2 clinically significant bleeding or < 10,000 platelets requiring platelet transfusion, or Grade ≥ 3 with clinically significant bleeding or requiring platelet transfusion. |
| Time Frame | Cycle 1, 28 days |
Outcome Measure Data
| Analysis Population Description |
|---|
| All enrolled participants who received at least 1 dose of any study treatment |
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. |
| Measure Participants | 3 | 7 | 3 | 3 | 2 | 3 |
| Count of Participants [Participants] |
2
66.7%
|
2
28.6%
|
2
66.7%
|
0
0%
|
1
50%
|
0
0%
|
| Title | Number of Participants With Treatment-emergent Adverse Events (AEs) |
|---|---|
| Description | Adverse events (AEs) were graded using NCI-CTCAE (version 4.03) and according to the following: Grade 1 = mild AE, Grade 2 = Moderate AE, Grade 3 = a severe AE, Grade 4 = life-threatening AE, and Grade 5 = death due to AE. A serious AE is an event that met 1 or more of the following criteria: Death Life-threatening experience Required inpatient hospitalization or prolongation of an existing hospitalization Resulted in persistent or significant disability/incapacity A congenital anomaly birth defect in the offspring of an exposed female subject or offspring of a female partner of a male subject Important medical events that, based upon appropriate medical judgment, jeopardized the participant and may have required medical or surgical intervention to prevent an outcome listed above. Treatment-related AEs are those considered related to at least 1 study drug by the investigator. |
| Time Frame | From first dose of any study treatment to 30 days after last dose; median duration of treatment was 29.1, 12.4, 11.3, 66.6, 7.8, and 46.4 weeks in each treatment group, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of any study treatment |
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. |
| Measure Participants | 3 | 7 | 3 | 3 | 2 | 3 |
| Any treatment-emergent adverse event (TEAE) |
3
100%
|
7
100%
|
3
100%
|
3
100%
|
2
100%
|
3
100%
|
| TEAE ≥ grade 3 |
3
100%
|
6
85.7%
|
3
100%
|
3
100%
|
2
100%
|
2
66.7%
|
| Serious adverse events |
2
66.7%
|
4
57.1%
|
3
100%
|
2
66.7%
|
1
50%
|
1
33.3%
|
| TEAEs leading to discontinuation of study drug |
1
33.3%
|
1
14.3%
|
2
66.7%
|
1
33.3%
|
1
50%
|
0
0%
|
| Fatal adverse events |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Treatment-related adverse events (TRAE) |
3
100%
|
7
100%
|
3
100%
|
3
100%
|
2
100%
|
3
100%
|
| TRAE ≥ grade 3 |
3
100%
|
6
85.7%
|
2
66.7%
|
2
66.7%
|
2
100%
|
2
66.7%
|
| Treatment-related serious adverse events |
2
66.7%
|
4
57.1%
|
2
66.7%
|
1
33.3%
|
1
50%
|
1
33.3%
|
| TRAEs leading to discontinuation of study drug |
1
33.3%
|
1
14.3%
|
2
66.7%
|
1
33.3%
|
1
50%
|
0
0%
|
| Title | Plasma Oprozomib Concentration |
|---|---|
| Description | Plasma samples for oprozomib concentration assays were only collected for participants in the 5/14 dosing schedule groups. Oprozomib plasma concentrations were determined using liquid chromatography with tandem mass spectrometry. |
| Time Frame | Cycle 1 day 1 at 1 to 2.5 hours and 2.75 to 5 hours after end of infusion (EOI) and cycle 3 day 1 at predose and 1 to 2.5 hours and 2.75 to 5 hours after EOI. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants in the 5/14 dosing schedule groups with available concentration data |
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone |
|---|---|---|---|
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. |
| Measure Participants | 2 | 4 | 3 |
| Cycle 1 day 1, 1 - 2.5 hours post EOI |
497
(NA)
|
632
(657)
|
697
(435)
|
| Cycle 1 day 1, 2.75 - 5 hours post EOI |
299
(NA)
|
15.8
(NA)
|
78.0
(48.9)
|
| Cycle 3 day 1, predose |
0.0
|
142
(285)
|
0.0
(NA)
|
| Cycle 3 day 1, 1 - 2.5 hours post EOI |
111
(NA)
|
175
(303)
|
178
(NA)
|
| Cycle 3 day 1, 2.75 - 5 hours post EOI |
2.00
(NA)
|
255
(323)
|
69.1
(NA)
|
| Title | Overall Response Rate (ORR) |
|---|---|
| Description | ORR is defined as the percentage of participants with a best overall response of partial response (PR), very good PR (VGPR), complete response (CR), or stringent CR (sCR) based on the International Myeloma Working Group Uniform Response Criteria. PR: ≥ 50% reduction of serum M-protein and ≥ 90% reduction in urine M-protein or to < 200 mg/24 hrs, or a ≥ 50% decrease in dFLC. A ≥ 50% decrease in the size of soft tissue plasmacytomas present at baseline. VGPR: Serum and urine M-protein detectable by immunofixation but not electrophoresis or ≥ 90% decrease in serum M-protein with urine M-protein <100 mg/24 hrs. If disease measurable only by SFLC, ≥ 90% decrease in the difference between involved and uninvolved FLC levels (dFLC). CR: No immunofixation on serum and urine, disappearance of soft tissue plasmacytomas and <5% plasma cells in BM. Normal serum free light chain (SFLC) ratio if disease measurable only by SFLC. sCR: As for CR, and absence of clonal plasma cells in bone marrow (BM). |
| Time Frame | Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median duration of treatment at the analysis cutoff date of 18 July 2016 was 29.1, 12.4, 11.3, 66.6, 7.8 and 46.4 weeks in each group, respectively |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of any study treatment |
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. |
| Measure Participants | 3 | 7 | 3 | 3 | 2 | 3 |
| Number (95% Confidence Interval) [percentage of participants] |
66.7
2223.3%
|
57.1
815.7%
|
66.7
2223.3%
|
100.0
3333.3%
|
50.0
2500%
|
100.0
3333.3%
|
| Title | Duration of Response (DOR) |
|---|---|
| Description | Duration of response was defined as the time from first evidence of partial response (PR) or better to confirmation of disease progression or death due to any cause. Median DOR was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment. |
| Time Frame | Disease response was assessed every 4 weeks for 24 cycles then every 8 weeks until end of treatment; median time on follow-up at the analysis cut-off date of 18 July 2016 was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively. |
Outcome Measure Data
| Analysis Population Description |
|---|
| Participants who received at least 1 dose of any study treatment and who achieved a best overall response of sCR, CR, VGPR, or PR. |
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. |
| Measure Participants | 2 | 4 | 2 | 3 | 1 | 3 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
| Title | Progression-Free Survival (PFS) |
|---|---|
| Description | Progression-free survival is defined as the time from the start of treatment to disease progression or death (due to any cause), whichever occurred first. Median PFS was estimated using Kaplan-Meier methods. Participants who started a new anticancer therapy before documentation of disease progression or death, or who were alive without documentation of disease progression before the data cut-off date or who died or had disease progression immediately after more than 1 consecutively missed disease assessment visit were censored at the date of last disease assessment. |
| Time Frame | From first dose of study drug through the data cut-off date of 18 July 2016; median time on follow-up was 14.1, 3.5, 2.6, 16.0, 3.6, and 11.2 months in each group, respectively |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received at least 1 dose of any study treatment. |
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. |
| Measure Participants | 3 | 7 | 3 | 3 | 2 | 3 |
| Median (95% Confidence Interval) [months] |
NA
|
NA
|
NA
|
NA
|
NA
|
NA
|
Adverse Events
| Time Frame | From enrollment (for all-cause mortality) or from first dose of any study treatment (for adverse events) to 30 days after last dose; median duration of treatment was 29.14, 12.43, 11.29, 66.57, 7.79, and 46.43 weeks in each treatment group, respectively. | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||
| Arm/Group Title | Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | ||||||
| Arm/Group Description | Participants received oprozomib 150 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 180 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1 to 5 and days 15 to 19 (5/14 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 240 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with lenalidomide 25 mg on days 1 through 21 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 24 cycles, whichever occurred first. After completing 24 cycles of treatment, participants with stable disease or better could have continued on oprozomib with or without dexamethasone pretreatment. | Participants received oprozomib 210 mg once daily on days 1, 2, 8, 9, 15, 16, 22, and 23 (2/7 schedule) of each 28-day treatment cycle, in combination with oral cyclophosphamide 300 mg/m² on days 1, 8, and 15 and dexamethasone 20 mg/day on days 1, 2, 8, 9, 15, 16, 22, and 23, until progression of disease, unacceptable toxicity, or for 8 cycles, whichever occurred first. After completing 8 cycles of treatment, participants with stable disease or better were to continue on oprozomib with dexamethasone premedication for a total of 24 cycles or until progression of disease or unacceptable toxicity. After completing 24 cycles of treatment, participants without evidence of disease progression could have continued on oprozomib with or without dexamethasone pretreatment. | ||||||
All Cause Mortality |
||||||||||||
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | |||||||
| 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%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
Serious Adverse Events |
||||||||||||
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | |||||||
| 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 | 2/3 (66.7%) | 4/7 (57.1%) | 3/3 (100%) | 2/3 (66.7%) | 1/2 (50%) | 1/3 (33.3%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Febrile neutropenia | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Leukopenia | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neutropenia | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Cardiac disorders | ||||||||||||
| Bradycardia | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Myocardial infarction | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal pain upper | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Diarrhoea | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Nausea | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pancreatitis | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Upper gastrointestinal haemorrhage | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| General disorders | ||||||||||||
| Disease progression | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Bacterial sepsis | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Bronchitis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Cellulitis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Gastroenteritis viral | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Lung infection | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neutropenic infection | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neutropenic sepsis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pneumonia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Sepsis | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Urinary tract infection | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Fall | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Laceration | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Investigations | ||||||||||||
| Electrocardiogram QT prolonged | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Platelet count decreased | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Hyperglycaemia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Hypophosphataemia | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Muscular weakness | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Nervous system disorders | ||||||||||||
| Myoclonus | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Syncope | 0/3 (0%) | 0/7 (0%) | 2/3 (66.7%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Renal failure | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Pulmonary embolism | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Capillary leak syndrome | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Deep vein thrombosis | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hypotension | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
Other (Not Including Serious) Adverse Events |
||||||||||||
| Oprozomib 150 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 180 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 5/14 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 240 mg 2/7 + Lenalidomide + Dexamethasone | Oprozomib 210 mg 2/7 + Cyclophosphamide + Dexamethasone | |||||||
| 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%) | 7/7 (100%) | 3/3 (100%) | 3/3 (100%) | 2/2 (100%) | 3/3 (100%) | ||||||
| Blood and lymphatic system disorders | ||||||||||||
| Anaemia | 1/3 (33.3%) | 1/7 (14.3%) | 1/3 (33.3%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Leukopenia | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Lymphopenia | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neutropenia | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Thrombocytopenia | 1/3 (33.3%) | 2/7 (28.6%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Cardiac disorders | ||||||||||||
| Bradycardia | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Palpitations | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Tachycardia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 2/3 (66.7%) | ||||||
| Ear and labyrinth disorders | ||||||||||||
| Ear pain | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Eye disorders | ||||||||||||
| Dry eye | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Vision blurred | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 2/3 (66.7%) | ||||||
| Gastrointestinal disorders | ||||||||||||
| Abdominal distension | 0/3 (0%) | 2/7 (28.6%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 2/3 (66.7%) | ||||||
| Abdominal pain | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Cheilitis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Constipation | 1/3 (33.3%) | 4/7 (57.1%) | 1/3 (33.3%) | 2/3 (66.7%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Diarrhoea | 2/3 (66.7%) | 5/7 (71.4%) | 3/3 (100%) | 3/3 (100%) | 1/2 (50%) | 2/3 (66.7%) | ||||||
| Dry mouth | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Dyspepsia | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 3/3 (100%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Faecaloma | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Flatulence | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Gastrointestinal toxicity | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Gastrooesophageal reflux disease | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Haemorrhoids | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Melaena | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Nausea | 3/3 (100%) | 6/7 (85.7%) | 2/3 (66.7%) | 3/3 (100%) | 2/2 (100%) | 2/3 (66.7%) | ||||||
| Stomatitis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Vomiting | 2/3 (66.7%) | 3/7 (42.9%) | 2/3 (66.7%) | 3/3 (100%) | 1/2 (50%) | 0/3 (0%) | ||||||
| General disorders | ||||||||||||
| Asthenia | 0/3 (0%) | 2/7 (28.6%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Chills | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Fatigue | 2/3 (66.7%) | 4/7 (57.1%) | 1/3 (33.3%) | 3/3 (100%) | 1/2 (50%) | 1/3 (33.3%) | ||||||
| Gait disturbance | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Non-cardiac chest pain | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Oedema | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Oedema peripheral | 1/3 (33.3%) | 1/7 (14.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Pain | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Peripheral swelling | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pyrexia | 2/3 (66.7%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Thirst | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Xerosis | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Infections and infestations | ||||||||||||
| Bronchitis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Candida infection | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Cellulitis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Folliculitis | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Herpes zoster | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Nasopharyngitis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pharyngitis | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pneumonia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Sinusitis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Skin infection | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Tinea infection | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Upper respiratory tract infection | 2/3 (66.7%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 2/3 (66.7%) | ||||||
| Urinary tract infection | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Viral infection | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Injury, poisoning and procedural complications | ||||||||||||
| Compression fracture | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Contusion | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Fall | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Lumbar vertebral fracture | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Tooth fracture | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Wound | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Investigations | ||||||||||||
| Alanine aminotransferase increased | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Aspartate aminotransferase decreased | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Aspartate aminotransferase increased | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Blood alkaline phosphatase decreased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood alkaline phosphatase increased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Blood bicarbonate decreased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood bilirubin increased | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood chloride increased | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood creatinine increased | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood lactate dehydrogenase decreased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood lactate dehydrogenase increased | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood phosphorus increased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood pressure increased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Blood urea increased | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blood uric acid decreased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Carbon dioxide increased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Lymphocyte count decreased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neutrophil count decreased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neutrophil count increased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Protein total decreased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Red blood cell count decreased | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Weight decreased | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| White blood cell count decreased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| White blood cell count increased | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Metabolism and nutrition disorders | ||||||||||||
| Appetite disorder | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Decreased appetite | 0/3 (0%) | 3/7 (42.9%) | 0/3 (0%) | 2/3 (66.7%) | 1/2 (50%) | 1/3 (33.3%) | ||||||
| Dehydration | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hyperglycaemia | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Hyperkalaemia | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hypermagnesaemia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hypernatraemia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Hypoalbuminaemia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hypocalcaemia | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 2/3 (66.7%) | 1/2 (50%) | 1/3 (33.3%) | ||||||
| Hypoglycaemia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Hypokalaemia | 2/3 (66.7%) | 2/7 (28.6%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Hypomagnesaemia | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hyponatraemia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/2 (50%) | 1/3 (33.3%) | ||||||
| Hypophosphataemia | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||
| Arthralgia | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Back pain | 2/3 (66.7%) | 1/7 (14.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Bone pain | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Coccydynia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Groin pain | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Joint range of motion decreased | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Joint swelling | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Muscle spasms | 0/3 (0%) | 1/7 (14.3%) | 1/3 (33.3%) | 2/3 (66.7%) | 0/2 (0%) | 2/3 (66.7%) | ||||||
| Muscular weakness | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 1/2 (50%) | 1/3 (33.3%) | ||||||
| Musculoskeletal chest pain | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Musculoskeletal pain | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Myalgia | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neck pain | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pain in extremity | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||
| Polycythaemia vera | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Seborrhoeic keratosis | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Squamous cell carcinoma | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Nervous system disorders | ||||||||||||
| Burning sensation | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Dizziness | 1/3 (33.3%) | 4/7 (57.1%) | 2/3 (66.7%) | 2/3 (66.7%) | 1/2 (50%) | 2/3 (66.7%) | ||||||
| Dizziness postural | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Dysgeusia | 1/3 (33.3%) | 0/7 (0%) | 2/3 (66.7%) | 2/3 (66.7%) | 1/2 (50%) | 1/3 (33.3%) | ||||||
| Headache | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 2/3 (66.7%) | ||||||
| Hypoaesthesia | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Memory impairment | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Neuropathy peripheral | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Paraesthesia | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Peripheral sensory neuropathy | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Presyncope | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Tremor | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 3/3 (100%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Psychiatric disorders | ||||||||||||
| Claustrophobia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Confusional state | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Depressed mood | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Insomnia | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 2/3 (66.7%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Irritability | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Sleep disorder | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Renal and urinary disorders | ||||||||||||
| Acute kidney injury | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Dysuria | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pollakiuria | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Polyuria | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Renal failure | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Urinary retention | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Reproductive system and breast disorders | ||||||||||||
| Genital rash | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||
| Cough | 1/3 (33.3%) | 0/7 (0%) | 1/3 (33.3%) | 3/3 (100%) | 2/2 (100%) | 1/3 (33.3%) | ||||||
| Dry throat | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Dysphonia | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 3/3 (100%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Dyspnoea | 1/3 (33.3%) | 2/7 (28.6%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 2/3 (66.7%) | ||||||
| Dyspnoea exertional | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Epistaxis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hiccups | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Nasal congestion | 0/3 (0%) | 0/7 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Oropharyngeal pain | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pleural effusion | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Productive cough | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 2/3 (66.7%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pulmonary oedema | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Rhinorrhoea | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Sinus congestion | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Tachypnoea | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Throat irritation | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Skin and subcutaneous tissue disorders | ||||||||||||
| Acne | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Blister | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Dry skin | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Ecchymosis | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Erythema | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hyperhidrosis | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Pruritus | 0/3 (0%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Rash | 1/3 (33.3%) | 1/7 (14.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Rash macular | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Vascular disorders | ||||||||||||
| Aortic arteriosclerosis | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Hot flush | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 1/3 (33.3%) | ||||||
| Hypertension | 0/3 (0%) | 0/7 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/2 (50%) | 0/3 (0%) | ||||||
| Hypotension | 1/3 (33.3%) | 1/7 (14.3%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/2 (0%) | 0/3 (0%) | ||||||
| Orthostatic hypotension | 1/3 (33.3%) | 0/7 (0%) | 0/3 (0%) | 0/3 (0%) | 0/2 (0%) | 0/3 (0%) | ||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Results Point of Contact
| Name/Title | Study Director |
|---|---|
| Organization | Amgen Inc. |
| Phone | 866-572-6436 |
| medinfo@amgen.com |
Responsible Party:
Amgen
ClinicalTrials.gov Identifier:
NCT01881789
Other Study ID Numbers:
- OPZ003
- 20130410
First Posted:
Jun 20, 2013
Last Update Posted:
Mar 25, 2021
Last Verified:
Feb 1, 2021