Vorinostat (MK-0683, SAHA [Suberoylanilide Hydroxamic Acid]) + Lenalidomide + Dexamethasone in Multiple Myeloma (MM) (MK-0683-074)
Sponsor
Merck Sharp & Dohme Corp. (Industry)
Overall Status
Completed
CT.gov ID
NCT00642954
Collaborator
(none)
31
5
66.2
Study Details
Study Description
Brief Summary
The purpose of this Phase I study of vorinostat in combination with lenalidomide and dexamethasone in participants with relapsed or refractory multiple myeloma is to determine the maximum tolerated dose (MTD) as estimated by the incidence of dose-limiting toxicities (DLTs) and recommended Phase 2 dose (RP2D) as estimated by the incidence of drug-related adverse events (AEs).
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
| Phase 1 |
Study Design
Study Type:
Interventional
Actual Enrollment
:
31 participants
Allocation:
Non-Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Phase I Study of Vorinostat in Combination With Lenalidomide and Dexamethasone in Patients With Relapsed or Refractory Multiple Myeloma
Actual Study Start Date
:
Feb 13, 2008
Actual Primary Completion Date
:
Sep 3, 2012
Actual Study Completion Date
:
Aug 20, 2013
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Level 1: Vorinostat 300 mg + lenalidomide 10 mg Participants will receive vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity. |
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
|
| Experimental: Level 2: Vorinostat 400 mg + lenalidomide 10 mg Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity. |
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
|
| Experimental: Level 3: Vorinostat 400 mg + lenalidomide 15 mg Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity. |
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
|
| Experimental: Level 4: Vorinostat 400 mg + lenalidomide 20 mg Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity. |
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
|
| Experimental: Level 5: Vorinostat 400 mg + lenalidomide 25 mg Participants will receive vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. Qualified participants who don't have disease progression can continue treatment after 8 cycles at the same dose and schedule, until progressive disease or unacceptable toxicity. |
Drug: Vorinostat
Vorinostat 300 mg or 400 mg QD via oral capsule on Days 1-7 and Days 15-21 of each 28-day cycle.
Other Names:
Drug: Lenalidomide
Lenalidomide 10 mg, 15 mg, 20 mg or 25 mg QD via oral capsule on Days 1-21 of each 28-day cycle.
Other Names:
Drug: Dexamethasone
Dexamethasone 40 mg QD via oral tablet on Days 1, 8, 15 and 22 of each 28-day cycle.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) [Cycle 1 (Up to 28 days)]
DLTs consisted of hematologic or non-hemtologic toxicities. Hematologic DLT was any grade (gr) 4 neutropenia lasting ≥7 days, gr 4 thrombocytopenia or gr 5 hematologic toxicity. Non-hematologic DLT was any gr 3, 4 or 5 non-hematologic toxicity with the exception of (1) gr 3 nausea, vomiting, diarrhea or dehydration not compliant with medical care, lasting <48 hours (2) gr 3 acidosis/alkalosis returning to ≤ gr 2 by 48 hours of medical care (3) gr 3 liver function test elevation without symptoms, lasting ≤5 days (4) Gr 3 amylase elevation without symptoms (5) Gr 3 hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia or hyphosphatemia responding to medical care (6) Gr 3 hypercholeresterolemia or hypertriglyceridemia. A drug-related AE causing dose modification of study drug is also considered a DLT. Per protocol DLTs were analyzed in the first 28-day treatment cycle. The number of participants experiencing DLTs is reported here for all participants who got ≥1 dose of study drug.
Secondary Outcome Measures
- Number of Participants Experiencing Drug-Related Adverse Events (AEs) [Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)]
An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. An AE was considered related to a drug as determined by the investigator based on exposure (evidence of exposure to drug), time course (time of AE onset versus drug-induced effect), likely cause (AE etiology related or un-related to drug), de-challenge (drug dose reduction/discontinuation) or re-challenge (drug re-exposure). Per protocol participants experiencing drug-related AEs were analyzed at the time of the protocol-specified final statistical analysis with a 3-September (Sep)-2012 data cut-off. The number of participants experiencing drug-related AEs is reported here for all participants who got ≥1 dose of study drug.
Other Outcome Measures
- Number of Participants Experiencing Best Overall Response Determined by Complete Response (CR), Near Complete Response (NCR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD) [Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012)]
Best overall tumor response consisted of CR (negative M-protein immunofixation [IF], <5% bone marrow [BM] plasma cells, no soft tissue plasmacytomas [STP]), NCR (positive M-protein IF, <5% BM plasma cells, no STP), VGPR (≥90% M-protein decrease, <5% BM plasma cells, no STP), PR (≥50% M-protein, BM plasma cells, STP decrease), MR (25-49% M-protein, BM plasma cells, STP decrease), SD (<25% decrease-25% increase in M-protein, BM plasma cells; <25% decrease-increase in definite STP) or PD (≥25% M-protein, BM plasma cells increase; new STP, lesions). Per protocol participants experiencing best overall response by CR, NCR, VGPR, PR, MR, SD or PD were analyzed as a single prespecified analysis at the time of protocol-specified final statistical analysis with a 3-Sep-2012 data cut-off. The number of participants experiencing best overall response by CR, NCR, VGPR, PR, MR, SD or PD is reported here for all participants who got ≥1 dose of study drug and had a post baseline efficacy assessment.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion Criteria:
-
Is a male or female at least 18 years old
-
Has relapsed or refractory MM and has had at least one prior therapy
-
Female participants of childbearing potential must have 2 negative serum pregnancy tests prior to receiving the first dose of study drugs
-
Female participants who can become pregnant must agree to use 2 separate forms of effective birth control at the same time, 4 weeks before, while taking, and for 4 weeks after stopping lenalidomide; post menopausal participants should be free from menses for >2 years, or are surgically sterilized
-
Male participant agrees to use an adequate method of contraception for the duration of the study, even if the participant has undergone a successful vasectomy
-
Male participants must agree to use a latex condom during sexual contact with a pregnant female or a female who can become pregnant; this is required for the duration of the study, and for 4 weeks after stopping therapy
-
Has at least 3 weeks washout prior to treatment
-
Is able to swallow capsules and is able to take or tolerate oral medications on a continuous basis
Exclusion Criteria:
-
Has prior treatment with a histone deacetylase (HDAC) inhibitor
-
Has prior allogenetic bone marrow transplant
-
Has received intravenous antibiotics, antiviral, or antifungal agents within 2 weeks prior to the start of the study drug
-
Uses illicit drugs, substance abuse or had a recent history (within the last year) of drug or alcohol abuse
-
Is pregnant or breast feeding or expecting to have a baby during the course of the study
-
Has human immunodeficiency virus (HIV) infection
-
Has Hepatitis B/C infection
-
Is currently receiving treatment for another type of cancer other than skin or cervical cancer that has not been in remission for 5 years or longer
Contacts and Locations
Locations
No locations specified.Sponsors and Collaborators
- Merck Sharp & Dohme Corp.
Investigators
- Study Director: Medical Director, Merck Sharp & Dohme Corp.
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.Responsible Party:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00642954
Other Study ID Numbers:
- 0683-074
- 2007_511
- 2007-001033-34
- MK-0683-074
First Posted:
Mar 25, 2008
Last Update Posted:
Nov 18, 2020
Last Verified:
Oct 1, 2020
Individual Participant Data (IPD) Sharing Statement:
Yes
Plan to Share IPD:
Yes
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle. Treatment continued until progressive disease or unacceptable toxicity. |
| Period Title: Overall Study | |||||
| STARTED | 4 | 4 | 3 | 3 | 17 |
| COMPLETED | 0 | 0 | 0 | 0 | 1 |
| NOT COMPLETED | 4 | 4 | 3 | 3 | 16 |
Baseline Characteristics
| Arm/Group Title | Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg | Total |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants received vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle. Treatment continued until progressive disease or unacceptable toxicity. | Total of all reporting groups |
| Overall Participants | 4 | 4 | 3 | 3 | 17 | 31 |
| Age (Years) [Mean (Standard Deviation) ] | ||||||
| Mean (Standard Deviation) [Years] |
69.5
(4.7)
|
58.5
(2.1)
|
66.3
(6.1)
|
55.7
(2.5)
|
64.1
(7.2)
|
63.5
(7.0)
|
| Sex: Female, Male (Count of Participants) | ||||||
| Female |
2
50%
|
1
25%
|
2
66.7%
|
1
33.3%
|
7
41.2%
|
13
41.9%
|
| Male |
2
50%
|
3
75%
|
1
33.3%
|
2
66.7%
|
10
58.8%
|
18
58.1%
|
Outcome Measures
| Title | Number of Participants Experiencing Dose-Limiting Toxicities (DLTs) |
|---|---|
| Description | DLTs consisted of hematologic or non-hemtologic toxicities. Hematologic DLT was any grade (gr) 4 neutropenia lasting ≥7 days, gr 4 thrombocytopenia or gr 5 hematologic toxicity. Non-hematologic DLT was any gr 3, 4 or 5 non-hematologic toxicity with the exception of (1) gr 3 nausea, vomiting, diarrhea or dehydration not compliant with medical care, lasting <48 hours (2) gr 3 acidosis/alkalosis returning to ≤ gr 2 by 48 hours of medical care (3) gr 3 liver function test elevation without symptoms, lasting ≤5 days (4) Gr 3 amylase elevation without symptoms (5) Gr 3 hypocalcemia, hypokalemia, hypomagnesemia, hyponatremia or hyphosphatemia responding to medical care (6) Gr 3 hypercholeresterolemia or hypertriglyceridemia. A drug-related AE causing dose modification of study drug is also considered a DLT. Per protocol DLTs were analyzed in the first 28-day treatment cycle. The number of participants experiencing DLTs is reported here for all participants who got ≥1 dose of study drug. |
| Time Frame | Cycle 1 (Up to 28 days) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received ≥1 dose of study treatment. |
| Arm/Group Title | Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle. Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 4 | 4 | 3 | 3 | 17 |
| Count of Participants [Participants] |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.9%
|
| Title | Number of Participants Experiencing Drug-Related Adverse Events (AEs) |
|---|---|
| Description | An AE was defined as any unfavorable and unintended change in the structure, function or chemistry of the body temporally associated with the use of the Sponsor's product, whether or not considered related to the use of the product. Any worsening of a pre-existing condition which is temporally associated with the use of the Sponsor's product is also an AE. An AE was considered related to a drug as determined by the investigator based on exposure (evidence of exposure to drug), time course (time of AE onset versus drug-induced effect), likely cause (AE etiology related or un-related to drug), de-challenge (drug dose reduction/discontinuation) or re-challenge (drug re-exposure). Per protocol participants experiencing drug-related AEs were analyzed at the time of the protocol-specified final statistical analysis with a 3-September (Sep)-2012 data cut-off. The number of participants experiencing drug-related AEs is reported here for all participants who got ≥1 dose of study drug. |
| Time Frame | Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received ≥1 dose of study treatment. |
| Arm/Group Title | Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle. Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 4 | 4 | 3 | 3 | 17 |
| Count of Participants [Participants] |
2
50%
|
3
75%
|
3
100%
|
3
100%
|
17
100%
|
| Title | Number of Participants Experiencing Best Overall Response Determined by Complete Response (CR), Near Complete Response (NCR), Very Good Partial Response (VGPR), Partial Response (PR), Minimal Response (MR), Stable Disease (SD) or Progressive Disease (PD) |
|---|---|
| Description | Best overall tumor response consisted of CR (negative M-protein immunofixation [IF], <5% bone marrow [BM] plasma cells, no soft tissue plasmacytomas [STP]), NCR (positive M-protein IF, <5% BM plasma cells, no STP), VGPR (≥90% M-protein decrease, <5% BM plasma cells, no STP), PR (≥50% M-protein, BM plasma cells, STP decrease), MR (25-49% M-protein, BM plasma cells, STP decrease), SD (<25% decrease-25% increase in M-protein, BM plasma cells; <25% decrease-increase in definite STP) or PD (≥25% M-protein, BM plasma cells increase; new STP, lesions). Per protocol participants experiencing best overall response by CR, NCR, VGPR, PR, MR, SD or PD were analyzed as a single prespecified analysis at the time of protocol-specified final statistical analysis with a 3-Sep-2012 data cut-off. The number of participants experiencing best overall response by CR, NCR, VGPR, PR, MR, SD or PD is reported here for all participants who got ≥1 dose of study drug and had a post baseline efficacy assessment. |
| Time Frame | Up to ~55 months (through pre-specified final statistical analysis cut-off date of 3-Sep-2012) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All participants who received ≥1 dose of study treatment and had a post baseline efficacy assessment. |
| Arm/Group Title | Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg |
|---|---|---|---|---|---|
| Arm/Group Description | Participants received vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle. Treatment continued until progressive disease or unacceptable toxicity. |
| Measure Participants | 4 | 4 | 3 | 3 | 16 |
| CR |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
1
5.9%
|
| NCR |
0
0%
|
1
25%
|
0
0%
|
0
0%
|
0
0%
|
| VGPR |
1
25%
|
0
0%
|
0
0%
|
1
33.3%
|
2
11.8%
|
| PR |
1
25%
|
1
25%
|
0
0%
|
1
33.3%
|
5
29.4%
|
| MR |
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
2
11.8%
|
| SD |
1
25%
|
1
25%
|
1
33.3%
|
0
0%
|
5
29.4%
|
| PD |
1
25%
|
1
25%
|
1
33.3%
|
1
33.3%
|
1
5.9%
|
Adverse Events
| Time Frame | Up to ~66 months (through database cut-off date of 20-August-2013) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | Safety was analyzed in all participants who received ≥1 dose of study drug. Per protocol disease progression of cancer under study was not considered an AE unless considered related to study drug. Therefore Medical Dictionary for Regulatory Activities (MedDRA) preferred terms "Neoplasm progression", "Malignant neoplasm progression" and "Disease progression" not related to study drug are excluded as AEs. | |||||||||
| Arm/Group Title | Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg | |||||
| Arm/Group Description | Participants received vorinostat 300 mg orally once-daily (QD) on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 10 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 15 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 20 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle for up to 8 cycles. | Participants received vorinostat 400 mg orally QD on Days 1-7 and Days 15-21; lenalidomide 25 mg orally QD on Days 1-21 and dexamethasone 40 mg orally QD on Days 1, 8, 15 and 22 of each 28-day cycle. Treatment continued until progressive disease or unacceptable toxicity. | |||||
All Cause Mortality |
||||||||||
| Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 0/4 (0%) | 1/4 (25%) | 0/3 (0%) | 0/3 (0%) | 3/17 (17.6%) | |||||
Serious Adverse Events |
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| Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 2/4 (50%) | 1/4 (25%) | 1/3 (33.3%) | 2/3 (66.7%) | 8/17 (47.1%) | |||||
| Cardiac disorders | ||||||||||
| Extrasystoles | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Myocardial infarction | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Gastrointestinal disorders | ||||||||||
| Diarrhoea | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 2 | 1/17 (5.9%) | 1 |
| General disorders | ||||||||||
| Chest pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Pyrexia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Hepatobiliary disorders | ||||||||||
| Acute hepatic failure | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Infections and infestations | ||||||||||
| Bronchitis viral | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Diverticulitis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Pneumonia | 1/4 (25%) | 2 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 3 |
| Pyelonephritis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Sepsis | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Septic shock | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Soft tissue infection | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Injury, poisoning and procedural complications | ||||||||||
| Accidental overdose | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Sternal fracture | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Investigations | ||||||||||
| Electrocardiogram QT prolonged | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Troponin I increased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Metabolism and nutrition disorders | ||||||||||
| Dehydration | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Head and neck cancer | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nervous system disorders | ||||||||||
| Syncope | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Psychiatric disorders | ||||||||||
| Confusional state | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Acute pulmonary oedema | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Cough | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Epistaxis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypoxia | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Pulmonary embolism | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Vascular disorders | ||||||||||
| Deep vein thrombosis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
Other (Not Including Serious) Adverse Events |
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| Level 1: Vorinostat 300 mg + Lenalidomide 10 mg | Level 2: Vorinostat 400 mg + Lenalidomide 10 mg | Level 3: Vorinostat 400 mg + Lenalidomide 15 mg | Level 4: Vorinostat 400 mg + Lenalidomide 20 mg | Level 5: Vorinostat 400 mg + Lenalidomide 25 mg | ||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 4/4 (100%) | 4/4 (100%) | 3/3 (100%) | 3/3 (100%) | 17/17 (100%) | |||||
| Blood and lymphatic system disorders | ||||||||||
| Anaemia | 4/4 (100%) | 11 | 1/4 (25%) | 2 | 1/3 (33.3%) | 8 | 3/3 (100%) | 4 | 9/17 (52.9%) | 28 |
| Leukopenia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/17 (17.6%) | 10 |
| Lymphopenia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/17 (17.6%) | 9 |
| Neutropenia | 2/4 (50%) | 7 | 2/4 (50%) | 3 | 1/3 (33.3%) | 8 | 2/3 (66.7%) | 11 | 6/17 (35.3%) | 37 |
| Thrombocytopenia | 2/4 (50%) | 9 | 2/4 (50%) | 4 | 1/3 (33.3%) | 8 | 1/3 (33.3%) | 1 | 12/17 (70.6%) | 70 |
| Cardiac disorders | ||||||||||
| Angina pectoris | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Bradycardia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Extrasystoles | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Palpitations | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Ear and labyrinth disorders | ||||||||||
| Ear pain | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Tinnitus | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Eye disorders | ||||||||||
| Periorbital oedema | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Vision blurred | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/17 (17.6%) | 5 |
| Gastrointestinal disorders | ||||||||||
| Abdominal discomfort | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Abdominal pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Abdominal pain upper | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Breath odour | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Constipation | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 6/17 (35.3%) | 7 |
| Diarrhoea | 2/4 (50%) | 2 | 3/4 (75%) | 5 | 2/3 (66.7%) | 2 | 1/3 (33.3%) | 3 | 7/17 (41.2%) | 20 |
| Dry mouth | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 2 |
| Dyspepsia | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 2/17 (11.8%) | 2 |
| Dysphagia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Faeces discoloured | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Flatulence | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Gastrointestinal pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Gingival pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/17 (5.9%) | 1 |
| Haemorrhoids | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Hypoaesthesia oral | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypoaesthesia teeth | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nausea | 1/4 (25%) | 2 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 6/17 (35.3%) | 14 |
| Odynophagia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Oral discomfort | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Oral pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Post-tussive vomiting | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Rectal haemorrhage | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Tooth loss | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Toothache | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Vomiting | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/17 (17.6%) | 3 |
| General disorders | ||||||||||
| Asthenia | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 5/17 (29.4%) | 10 |
| Chest discomfort | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Chest pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Chills | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Cyst | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 2 |
| Fatigue | 2/4 (50%) | 2 | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 11/17 (64.7%) | 60 |
| Feeling jittery | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Gait disturbance | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 3 |
| Local swelling | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Malaise | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Mass | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Medical device complication | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 2 |
| Oedema peripheral | 1/4 (25%) | 3 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 3/17 (17.6%) | 3 |
| Pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Pyrexia | 0/4 (0%) | 0 | 2/4 (50%) | 3 | 2/3 (66.7%) | 3 | 0/3 (0%) | 0 | 4/17 (23.5%) | 6 |
| Infections and infestations | ||||||||||
| Bronchitis | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Cellulitis | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Ear infection | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Hepatitis B | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Herpes zoster | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Influenza | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Laryngitis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Nasopharyngitis | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/17 (17.6%) | 3 |
| Pharyngitis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Pneumonia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Pneumonia primary atypical | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Rhinitis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Sinusitis | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Tooth infection | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Upper respiratory tract infection | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 2/3 (66.7%) | 4 | 1/3 (33.3%) | 5 | 5/17 (29.4%) | 7 |
| Urinary tract infection | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Viral infection | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Injury, poisoning and procedural complications | ||||||||||
| Accidental overdose | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Bone fragmentation | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Contusion | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/17 (11.8%) | 2 |
| Electric shock | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Fall | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Laceration | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Rib fracture | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Tendon rupture | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Investigations | ||||||||||
| Activated partial thromboplastin time prolonged | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 5 |
| Alanine aminotransferase increased | 0/4 (0%) | 0 | 2/4 (50%) | 5 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 3/17 (17.6%) | 9 |
| Aspartate aminotransferase increased | 1/4 (25%) | 1 | 2/4 (50%) | 4 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 2/17 (11.8%) | 9 |
| Blood alkaline phosphatase increased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Blood bilirubin increased | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Blood calcium decreased | 2/4 (50%) | 3 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Blood calcium increased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Blood creatinine increased | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 5/17 (29.4%) | 23 |
| Blood glucose increased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Blood lactate dehydrogenase increased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 2 |
| Blood magnesium decreased | 3/4 (75%) | 5 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 2/3 (66.7%) | 2 | 2/17 (11.8%) | 4 |
| Blood phosphorus decreased | 1/4 (25%) | 5 | 3/4 (75%) | 3 | 2/3 (66.7%) | 2 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Blood potassium increased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Blood urea increased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 9 |
| Blood uric acid increased | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Electrocardiogram abnormal | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Gamma-glutamyltransferase increased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 5 |
| Haematocrit decreased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Haemoglobin decreased | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/17 (11.8%) | 5 |
| International normalised ratio increased | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/17 (17.6%) | 8 |
| Neutrophil count decreased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/17 (5.9%) | 1 |
| Platelet count decreased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 4 | 1/17 (5.9%) | 4 |
| Prothrombin time prolonged | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 5 |
| Weight decreased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 2/17 (11.8%) | 3 |
| Metabolism and nutrition disorders | ||||||||||
| Decreased appetite | 2/4 (50%) | 2 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 1 | 4/17 (23.5%) | 5 |
| Diabetes mellitus | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 5 |
| Gout | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hyperglycaemia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 4/17 (23.5%) | 23 |
| Hyperphosphataemia | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hyperuricaemia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypoalbuminaemia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 5 |
| Hypocalcaemia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/17 (23.5%) | 9 |
| Hypoglycaemia | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 3 |
| Hypokalaemia | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypomagnesaemia | 2/4 (50%) | 6 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Hyponatraemia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Hypophosphataemia | 1/4 (25%) | 2 | 2/4 (50%) | 2 | 1/3 (33.3%) | 2 | 0/3 (0%) | 0 | 3/17 (17.6%) | 11 |
| Musculoskeletal and connective tissue disorders | ||||||||||
| Back pain | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 3/3 (100%) | 3 | 0/3 (0%) | 0 | 5/17 (29.4%) | 7 |
| Bone pain | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/17 (5.9%) | 1 |
| Flank pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Intervertebral disc protrusion | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Joint range of motion decreased | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Muscle spasms | 0/4 (0%) | 0 | 2/4 (50%) | 3 | 1/3 (33.3%) | 2 | 2/3 (66.7%) | 2 | 7/17 (41.2%) | 13 |
| Musculoskeletal chest pain | 0/4 (0%) | 0 | 2/4 (50%) | 2 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Musculoskeletal discomfort | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Musculoskeletal pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Myalgia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/17 (17.6%) | 11 |
| Neck pain | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Osteoarthritis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 2 |
| Osteonecrosis of jaw | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 1/17 (5.9%) | 1 |
| Pain in extremity | 1/4 (25%) | 4 | 1/4 (25%) | 1 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 4/17 (23.5%) | 5 |
| Pain in jaw | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||
| Lung neoplasm | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nervous system disorders | ||||||||||
| Balance disorder | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Dizziness | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/17 (23.5%) | 20 |
| Dysgeusia | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 3/17 (17.6%) | 4 |
| Headache | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 2/3 (66.7%) | 2 | 4/17 (23.5%) | 6 |
| Hyperaesthesia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Hypoaesthesia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Lethargy | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Neuropathy peripheral | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 5/17 (29.4%) | 6 |
| Paraesthesia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Parkinson's disease | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Peripheral sensory neuropathy | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 3/17 (17.6%) | 16 |
| Sciatica | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Tremor | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 4 |
| Psychiatric disorders | ||||||||||
| Agitation | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Anxiety | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Confusional state | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Depression | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Insomnia | 1/4 (25%) | 1 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 4/17 (23.5%) | 4 |
| Mood altered | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Mood swings | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Renal and urinary disorders | ||||||||||
| Pollakiuria | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Renal failure acute | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Renal impairment | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Reproductive system and breast disorders | ||||||||||
| Erectile dysfunction | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Prostatitis | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Respiratory, thoracic and mediastinal disorders | ||||||||||
| Cough | 3/4 (75%) | 4 | 2/4 (50%) | 3 | 1/3 (33.3%) | 2 | 1/3 (33.3%) | 1 | 7/17 (41.2%) | 9 |
| Dyspnoea | 2/4 (50%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 5/17 (29.4%) | 15 |
| Dyspnoea exertional | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Epistaxis | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 5/17 (29.4%) | 7 |
| Hiccups | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Nasal congestion | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Oropharyngeal pain | 1/4 (25%) | 1 | 2/4 (50%) | 2 | 1/3 (33.3%) | 1 | 1/3 (33.3%) | 2 | 3/17 (17.6%) | 3 |
| Productive cough | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 2 |
| Pulmonary congestion | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Respiratory tract congestion | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Rhinalgia | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Sinus congestion | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Sputum discoloured | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Wheezing | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Skin and subcutaneous tissue disorders | ||||||||||
| Alopecia | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Dry skin | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Exfoliative rash | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 1/3 (33.3%) | 1 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Petechiae | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Pruritus | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 4/17 (23.5%) | 7 |
| Rash | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 2/17 (11.8%) | 3 |
| Rash generalised | 0/4 (0%) | 0 | 1/4 (25%) | 1 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Skin lesion | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Swelling face | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 1 |
| Vascular disorders | ||||||||||
| Deep vein thrombosis | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Flushing | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 1/17 (5.9%) | 2 |
| Hot flush | 0/4 (0%) | 0 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Hypotension | 1/4 (25%) | 2 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
| Thrombophlebitis superficial | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 1/3 (33.3%) | 1 | 0/17 (0%) | 0 |
| Thrombosis | 1/4 (25%) | 1 | 0/4 (0%) | 0 | 0/3 (0%) | 0 | 0/3 (0%) | 0 | 0/17 (0%) | 0 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.
Results Point of Contact
| Name/Title | Senior Vice President, Global Clinical Development |
|---|---|
| Organization | Merck Sharp & Dohme Corp. |
| Phone | 1-800-672-6372 |
| ClinicalTrialsDisclosure@merck.com |
Responsible Party:
Merck Sharp & Dohme Corp.
ClinicalTrials.gov Identifier:
NCT00642954
Other Study ID Numbers:
- 0683-074
- 2007_511
- 2007-001033-34
- MK-0683-074
First Posted:
Mar 25, 2008
Last Update Posted:
Nov 18, 2020
Last Verified:
Oct 1, 2020