Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma
Sponsor
Janssen Research & Development, LLC (Industry)
Overall Status
Completed
CT.gov ID
NCT00574288
Collaborator
(none)
104
7
2
108.3
14.9
0.1
Study Details
Study Description
Brief Summary
Establishment of safety profile of HuMax-CD38 when given as monotherapy in participants with multiple myeloma relapsed from or refractory to at least 2 different cytoreductive therapies and without further established treatment options.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Detailed Description
This study is conducted in two parts. In part I, participants are enrolled into cohorts at increasing dose levels. Participant safety and efficacy during part I will determine the doses used for Part II. In part II participants will be enrolled into one of two sequential treatment arms using two of the doses defined in part 1 of the study. Part II was 5 cohorts, 3 with 8 milligram per kilogram (mg/kg) and 2 with 16 mg/kg. Part I and all but the last cohort in Part II were dosed with Phase 1/ 2 drug product. The last cohort in Part II was dosed with Phase 3 drug product. Both Part I and Part II are open-label/unmasked.
Study Design
Study Type:
Interventional
Actual Enrollment
:
104 participants
Allocation:
Non-Randomized
Intervention Model:
Single Group Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Daratumumab (HuMax®-CD38) Safety Study in Multiple Myeloma - Open Label, Dose-escalation Followed by Open Label, Single-arm Study
Actual Study Start Date
:
Mar 26, 2008
Actual Primary Completion Date
:
Jan 9, 2015
Actual Study Completion Date
:
Apr 3, 2017
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Dose Escalation: Daratumumab
|
Drug: Part 1: Daratumumab
First participant will receive intravenous (injection of a substance into a vein) 0.005 milligram per kilogram (mg/kg) (planned dose) infusion of daratumumab and other participants will receive different doses. The participants will receive 7 full infusions of daratumumab and 2 predose infusions every 2 weeks. The dose of daratumumab will be escalated sequentially and considering the safety and efficacy of dose in Part 1, dose for Part 2 of the study will be decided. A predose infusion of 10% of the full dose of daratumumab will be administered a day before the first 2 full infusions.
Other Names:
Other: Methylprednisolone
Pre-dose: Participants (part 1) will receive methylprednisolone 80 mg intravenous (IV) injection 30 minutes to 2 hours before treatment. Participants (part 2) will receive 100 mg methylprednisolone IV 60 minutes to 2 hours before treatment; if a patient experiences no significant infusion-related reactions, the dose of methylprednisolone may be decreased to 50 mg after Visit 4.
Post-dose: All participants (part 1) will receive 40 mg methylprednisolone orally on the first and the second day after all full infusions. During Part 2, all participants will receive 20-25 mg methylprednisolone orally or equivalent on the first and second days after all full-dose infusions.
|
| Experimental: Dose Expansion: Daratumumab
|
Drug: Part 2: Daratumumab
In Part 2, the participants will receive dose of daratumumab as determined in part 1 (16 mg/kg) of the study. Participants will receive 8 full infusions at weekly intervals followed by biweekly (every 2 weeks) infusions for 16 additional weeks and monthly infusions until disease progression or unmanageable toxicity, whichever comes first. Predose was dropped at some point in Part 2. A predose infusion of 10 mg daratumumab will be administered on the day before the first full infusion in select cohorts.
Other Names:
Other: Methylprednisolone
Pre-dose: Participants (part 1) will receive methylprednisolone 80 mg intravenous (IV) injection 30 minutes to 2 hours before treatment. Participants (part 2) will receive 100 mg methylprednisolone IV 60 minutes to 2 hours before treatment; if a patient experiences no significant infusion-related reactions, the dose of methylprednisolone may be decreased to 50 mg after Visit 4.
Post-dose: All participants (part 1) will receive 40 mg methylprednisolone orally on the first and the second day after all full infusions. During Part 2, all participants will receive 20-25 mg methylprednisolone orally or equivalent on the first and second days after all full-dose infusions.
Other: Dexamethasone
Participants (Part 2) will receive 20 mg dexamethasone intravenous (IV) injection pre-dose, on the first and second days after every full-dose infusions.
|
Outcome Measures
Primary Outcome Measures
- Number of Participants With Adverse Events [Up to Week 28 (for Part 1) and up to approximately 2.5 years (for Part 2)]
An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly.
Secondary Outcome Measures
- Overall Response Rate [Up to Week 28 (for Part 1) and Week 27 (for Part 2)]
Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein plus urine M-protein level < 100mg/24 hours; PR: >= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by >= 90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria.
- Part 1: Time to Response [Up to Week 28]
Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Kaplan-Meier method was used to estimate the distribution of time to response and time to best response.
- Part 2: Time to Progression (TTP) [Up to Week 27]
TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL); urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method.
- Part 2: Duration of Response as Assessed Using the Method of Kaplan-Meier [Up to Week 27]
Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria.
- Part 2: Progression-Free Survival [Up to Week 27]
Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first.
- Part 2: Time to Response [Up to Week 27]
Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Time to VGPR (very good partial response) was defined as the time from the date of first dose of daratumumab to the date of initial documentation of VGPR response. The Kaplan-Meier method was used to estimate time to response.
- Part 2: Overall Survival [Approximately 3 years]
Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method.
Eligibility Criteria
Criteria
Ages Eligible for Study:
18 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
Inclusion criteria
-
Diagnosis of multiple myeloma (MM) requiring systemic therapy
-
Age greater than or equal to (>=) 18 years
-
Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
-
Life expectancy greater than (>) 3 months
-
Relapsed from or refractory to two or more different prior therapies
-
Signed Informed consent
Exclusion criteria
-
Plasma cell leukemia defined as a plasma cell count > 2000/millimeter3 (mm3)
-
Known amyloidosis
-
Participants who previously have received an allogeneic stem cell transplant
-
Sensory or motor neuropathy of >= grade 3
-
Past or current malignancy
-
Chronic or ongoing active infectious disease
-
Clinically significant cardiac disease
-
Significant concurrent, uncontrolled medical condition including, but not limited to, renal (except related to MM), hepatic, hematological except MM, gastrointestinal, endocrine, pulmonary, neurological, cerebral or psychiatric disease
-
A baseline QT interval as corrected by Fridericia's formula > 470 millisecond (msec) for female participants or > 450 msec for male participants or a complete left bundle branch block (defined as a QRS interval >= 120 msec in left bundle branch block form)
-
Hypokalemia
-
Clinical signs of meningeal involvement of MM
-
Known severe chronic obstructive pulmonary disease or asthma defined as forced expiratory volume in 1 second (FEV1) less than (<) 60 percentage (%) of expected
-
History of significant cerebrovascular disease
-
Known Human Immunodeficiency Virus seropositivity
-
Positive serology for hepatitis B
-
Screening laboratory values
-
Concomitant corticosteroid
-
Other chemotherapy that is or may be active against myeloma within 3 weeks prior to Visit 2 (Part 1) or the first dose of daratumumab (Part 2). However, corticosteroid for myeloma (less than a 4-day course) could be administered within 1 week before Visit 2 (Part 1) or the first dose of daratumumab (Part 2)
-
Known hypersensitivity to components of the investigational product or severe allergic or anaphylactic reactions to humanized products
-
Participants who have received treatment with any nonmarket drug substance within 4 weeks before the first dose of daratumumab
-
Current participation in any other interventional clinical trial
-
Participants known or suspected of not being able to comply with a trial protocol (example, due to alcoholism, drug dependency, or psychological disorder)
-
Breastfeeding women or women with a positive pregnancy test at Screening
-
Women of childbearing potential not willing to use adequate contraception, defined as hormonal birth control or intrauterine device, during the trial and for 1 year after the last dose of daratumumab. For participants in the United States, the use of a double-barrier method is also considered adequate
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Boston | Massachusetts | United States | ||
| 2 | Copenhagen Ø | Denmark | |||
| 3 | Vejle | Denmark | |||
| 4 | Amsterdam | Netherlands | |||
| 5 | Utrecht | Netherlands | |||
| 6 | Huddinge | Sweden | |||
| 7 | Lund | Sweden |
Sponsors and Collaborators
- Janssen Research & Development, LLC
Investigators
- Study Director: Janssen Research & Development, LLC Clinical Trial, Janssen Research & Development, LLC
Study Documents (Full-Text)
None provided.More Information
Additional Information:
Publications
None provided.Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00574288
Other Study ID Numbers:
- CR101876
- GEN501
- DARA-GEN501
- 2007-003783-22
First Posted:
Dec 17, 2007
Last Update Posted:
Apr 27, 2018
Last Verified:
Mar 1, 2018
Studies a U.S. FDA-regulated Drug Product:
Yes
Studies a U.S. FDA-regulated Device Product:
No
Keywords provided by Janssen Research & Development, LLC
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail |
| Arm/Group Title | Part 1 - <4 mg/kg | Part 1 - 4 mg/kg | Part 1 - 8 mg/kg | Part 1 - 16 mg/kg | Part 1 - 24 mg/kg | Part 2 - 8 mg/kg | Part 2 - 16 mg/kg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Period Title: Overall Study | |||||||
| STARTED | 20 | 3 | 3 | 3 | 3 | 30 | 42 |
| COMPLETED | 0 | 0 | 0 | 1 | 1 | 4 | 14 |
| NOT COMPLETED | 20 | 3 | 3 | 2 | 2 | 26 | 28 |
Baseline Characteristics
| Arm/Group Title | Part 1 - <4 mg/kg | Part 1 - 4 mg/kg | Part 1 - 8 mg/kg | Part 1 - 16 mg/kg | Part 1 - 24 mg/kg | Part 2 - 8 mg/kg | Part 2 - 16 mg/kg | Total |
|---|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Total of all reporting groups |
| Overall Participants | 20 | 3 | 3 | 3 | 3 | 30 | 42 | 104 |
| Age (Count of Participants) | ||||||||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
11
55%
|
2
66.7%
|
2
66.7%
|
3
100%
|
2
66.7%
|
21
70%
|
22
52.4%
|
63
60.6%
|
| >=65 years |
9
45%
|
1
33.3%
|
1
33.3%
|
0
0%
|
1
33.3%
|
9
30%
|
20
47.6%
|
41
39.4%
|
| Age (years) [Mean (Standard Deviation) ] | ||||||||
| Mean (Standard Deviation) [years] |
61.8
(9.24)
|
64
(2)
|
61.3
(6.11)
|
53
(1.73)
|
59
(9.54)
|
58.6
(10.05)
|
63.8
(8.27)
|
61.4
(9)
|
| Sex: Female, Male (Count of Participants) | ||||||||
| Female |
7
35%
|
2
66.7%
|
0
0%
|
0
0%
|
0
0%
|
9
30%
|
15
35.7%
|
33
31.7%
|
| Male |
13
65%
|
1
33.3%
|
3
100%
|
3
100%
|
3
100%
|
21
70%
|
27
64.3%
|
71
68.3%
|
| Region of Enrollment (Count of Participants) | ||||||||
| Denmark |
11
55%
|
1
33.3%
|
2
66.7%
|
2
66.7%
|
0
0%
|
5
16.7%
|
9
21.4%
|
30
28.8%
|
| Netherlands |
4
20%
|
2
66.7%
|
1
33.3%
|
1
33.3%
|
2
66.7%
|
14
46.7%
|
8
19%
|
32
30.8%
|
| Sweden |
5
25%
|
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
5
16.7%
|
11
26.2%
|
22
21.2%
|
| United States |
0
0%
|
0
0%
|
0
0%
|
0
0%
|
0
0%
|
6
20%
|
14
33.3%
|
20
19.2%
|
| No. of Prior Lines of Therapy (Count of Participants) | ||||||||
| <= 3 Lines |
2
10%
|
2
66.7%
|
0
0%
|
0
0%
|
0
0%
|
6
20%
|
16
38.1%
|
26
25%
|
| > 3 Lines |
18
90%
|
1
33.3%
|
3
100%
|
3
100%
|
3
100%
|
24
80%
|
26
61.9%
|
78
75%
|
| Refractory to proteasome inhibitor (PI)/immunomodulatory agent (IMiD) (Count of Participants) | ||||||||
| Both a PI and IMiD |
0
0%
|
2
66.7%
|
3
100%
|
1
33.3%
|
2
66.7%
|
19
63.3%
|
27
64.3%
|
54
51.9%
|
| PI only |
0
0%
|
1
33.3%
|
0
0%
|
0
0%
|
0
0%
|
2
6.7%
|
3
7.1%
|
6
5.8%
|
| IMiD only |
0
0%
|
0
0%
|
0
0%
|
1
33.3%
|
1
33.3%
|
6
20%
|
4
9.5%
|
12
11.5%
|
| None |
20
100%
|
0
0%
|
0
0%
|
1
33.3%
|
0
0%
|
3
10%
|
8
19%
|
32
30.8%
|
Outcome Measures
| Title | Number of Participants With Adverse Events |
|---|---|
| Description | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. A serious adverse event (SAE) is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. |
| Time Frame | Up to Week 28 (for Part 1) and up to approximately 2.5 years (for Part 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. |
| Arm/Group Title | Part 1: Daratumumab Less Than (<) 4 mg/kg | Part 1: Daratumumab 4 mg/kg | Part 1:Daratumumab 8 mg/kg | Part 1: Daratumumab 16 mg/kg | Part 1:Daratumumab 24 mg/kg | Part 2: Daratumumab 8 mg/kg | Part 2: Daratumumab 16 mg/kg |
|---|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w), along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Measure Participants | 20 | 3 | 3 | 3 | 3 | 30 | 42 |
| Number [participants] |
19
95%
|
3
100%
|
3
100%
|
3
100%
|
3
100%
|
30
100%
|
41
97.6%
|
| Title | Overall Response Rate |
|---|---|
| Description | Overall response defined as percentage of participants who achieved stringent complete response (sCR), complete response (CR), very good partial response (VGPR) or partial response (PR). Per IMWG criteria, sCR: is defined as normal free light chain (FLC) ratio, and absence of clonal plasma cells (PCs) by immunohistochemistry, immunofluorescence or 2- to 4-color flow cytometry; CR: Negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and < 5 % plasma cells in bone marrow; VGPR: Serum and urine M-protein detectable by immunofixation but not on electrophoresis or >= 90% reduction in serum M-protein plus urine M-protein level < 100mg/24 hours; PR: >= 50 % reduction of serum M-protein and reduction in 24 hour urinary M-protein by >= 90% or to <200 mg/24 hours; if the serum and urine M-protein are not measurable, a decrease of >=50% in the difference between involved and uninvolved FLC levels is required in place of the M-protein criteria. |
| Time Frame | Up to Week 28 (for Part 1) and Week 27 (for Part 2) |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with >= 4 mg/kg daratumumab were used for efficacy analyses and less than (<) 4 mg/kg doses were considered under the therapeutic levels. |
| Arm/Group Title | Part 1: Daratumumab 4 mg/kg | Part 1:Daratumumab 8 mg/kg | Part 1: Daratumumab 16 mg/kg | Part 1:Daratumumab 24 mg/kg | Part 2: Daratumumab 8 mg/kg | Part 2: Daratumumab 16 mg/kg |
|---|---|---|---|---|---|---|
| Arm/Group Description | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w), along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Measure Participants | 3 | 3 | 3 | 3 | 30 | 42 |
| Number (95% Confidence Interval) [percentage of participants] |
33.3
166.5%
|
0
0%
|
33.3
1110%
|
66.7
2223.3%
|
10.0
333.3%
|
35.7
119%
|
| Title | Part 1: Time to Response |
|---|---|
| Description | Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Kaplan-Meier method was used to estimate the distribution of time to response and time to best response. |
| Time Frame | Up to Week 28 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. For Part 1, only participants treated with >= 4 mg/kg daratumumab were used for efficacy analyses and less than (<) 4 mg/kg doses were considered under the therapeutic levels. |
| Arm/Group Title | Part 1: Daratumumab 4 mg/kg | Daratumumab 8 mg/kg | Daratumumab 16 mg/kg | Part 1:Daratumumab 24 mg/kg |
|---|---|---|---|---|
| Arm/Group Description | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with participants received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with participants received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Measure Participants | 3 | 3 | 3 | 3 |
| Time to first response |
NA
|
NA
|
8.4
|
1.9
|
| Time to best response |
NA
|
NA
|
8.4
|
1.9
|
| Title | Part 2: Time to Progression (TTP) |
|---|---|
| Description | TTP was defined as the number of days from the date of first infusion (Day 1) to the date of first record of disease progression. Disease progression (IMWG criteria): increase of 25 percent (%) from lowest response level in Serum M-component and/or (the absolute increase must be >=0.5 g/dL); urine M-component and/or (the absolute increase must be >=200 mg/24 hour; only in participants without measurable serum and urine M-protein levels: the difference between involved and uninvolved free light chain levels (absolute increase must be >10 mg/dL); Development of hypercalcemia (corrected serum calcium >11.5 mg/dL or 2.65 mmol/L) that can be attributed solely to the plasma cell proliferative disorder. Median TTP was estimated by using the Kaplan-Meier method. |
| Time Frame | Up to Week 27 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. |
| Arm/Group Title | Daratumumab 8 mg/kg | Daratumumab 16 mg/kg |
|---|---|---|
| Arm/Group Description | Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Measure Participants | 30 | 42 |
| Median (95% Confidence Interval) [months] |
2.4
|
5.6
|
| Title | Part 2: Duration of Response as Assessed Using the Method of Kaplan-Meier |
|---|---|
| Description | Duration of response was calculated from the date of initial documentation of a response (PR or better) to the date of first documented evidence of progressive disease, as defined in the International Myeloma Working Group (IMWG) criteria. |
| Time Frame | Up to Week 27 |
Outcome Measure Data
| Analysis Population Description |
|---|
| Subset of All-Treated Analysis Set included those who had overall response in Part 2. |
| Arm/Group Title | Daratumumab 8 mg/kg | Daratumumab 16 mg/kg |
|---|---|---|
| Arm/Group Description | Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Measure Participants | 3 | 15 |
| Median (Full Range) [months] |
6.9
|
NA
|
| Title | Part 2: Progression-Free Survival |
|---|---|
| Description | Progression free survival (PFS) was defined as the time between the date of first dose of daratumumab and either disease progression or death, whichever occurs first. |
| Time Frame | Up to Week 27 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. |
| Arm/Group Title | Daratumumab 8 mg/kg | Daratumumab 16 mg/kg |
|---|---|---|
| Arm/Group Description | Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Measure Participants | 30 | 42 |
| Median (95% Confidence Interval) [months] |
2.4
|
5.6
|
| Title | Part 2: Time to Response |
|---|---|
| Description | Time to first response was defined as the time from the date of first dose of daratumumab to the date of initial documentation of a response (PR or better). Time to best response was defined as the time between the date of first dose of daratumumab and the date of the initial evaluation of the best response (PR or better) to treatment. Time to VGPR (very good partial response) was defined as the time from the date of first dose of daratumumab to the date of initial documentation of VGPR response. The Kaplan-Meier method was used to estimate time to response. |
| Time Frame | Up to Week 27 |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. Here 'n' (Number of Participants Analyzed) signifies number of participants analyzed at specific time point. |
| Arm/Group Title | Daratumumab 8 mg/kg | Daratumumab 16 mg/kg |
|---|---|---|
| Arm/Group Description | Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Measure Participants | 30 | 42 |
| Time to first response |
1.36
(0.774)
|
1.33
(0.955)
|
| Time to best response |
1.36
(0.774)
|
2.46
(2.800)
|
| Time to VGPR or better response |
0.49
(0.000)
|
| Title | Part 2: Overall Survival |
|---|---|
| Description | Overall Survival (OS) was defined as the number of days from administration of the first infusion (Day 1) to date of death. Median Overall Survival was estimated by using the Kaplan-Meier method. |
| Time Frame | Approximately 3 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| All-Treated Analysis Set included all enrolled participants who received at least 1 dose of study drug. |
| Arm/Group Title | Daratumumab 8 mg/kg | Daratumumab 16 mg/kg |
|---|---|---|
| Arm/Group Description | Participants were administered with 8 mg/kg daratumumab weekly once for 8 weeks, then every 2 week (q2w) for 16 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 week (q2w) for 14 weeks, then every 4 weeks (q4w) for up to 72 weeks or until the subject experienced disease progression or unmanageable toxicity, whichever came first (possible duration of treatment: 96 weeks). Along with methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. |
| Measure Participants | 30 | 42 |
| Median (95% Confidence Interval) [months] |
18.2
|
34.3
|
Adverse Events
| Time Frame | Up to Week 28 (for Part 1) and approximately 2.5 years | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Adverse Event Reporting Description | ||||||||||||||
| Arm/Group Title | Part 1 - <4 mg/kg | Part 1 - 4 mg/kg | Part 1 - 8 mg/kg | Part 1 - 16 mg/kg | Part 1 - 24 mg/kg | Part 2 - 8 mg/kg | Part 2 - 16 mg/kg | |||||||
| Arm/Group Description | Participants were administered with 7 full intravenous (IV) infusion of 0.005, 0.05, 0.1, 0.5, 1 and 2 milligram per kilogram body weight (mg/kg) daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 4 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 8 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 16 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 7 full IV infusion of 24 mg/kg daratumumab once weekly, along with this participants also received methylprednisolone 80 mg IV injection before first 2 infusions and 40 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | Participants were administered with 8 full IV infusions of 8 mg/kg daratumumab once weekly for 8 weeks, then every 2 weeks (q2w) for 16 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. | Participants were administered with 8 full IV infusions of 16 mg/kg daratumumab once weekly for 7 weeks, then every 2 weeks (q2w) for 14 weeks, then every 4 weeks (q4w) until the participant experienced disease progression or unmanageable toxicity whichever came first, along with this participants also received methylprednisolone 100 mg IV before treatment and 20-25 mg methylprednisolone orally for 2 days after all full infusions. First 2 infusions were separated by 3 week washout period. | |||||||
All Cause Mortality |
||||||||||||||
| Part 1 - <4 mg/kg | Part 1 - 4 mg/kg | Part 1 - 8 mg/kg | Part 1 - 16 mg/kg | Part 1 - 24 mg/kg | Part 2 - 8 mg/kg | Part 2 - 16 mg/kg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | / (NaN) | |||||||
Serious Adverse Events |
||||||||||||||
| Part 1 - <4 mg/kg | Part 1 - 4 mg/kg | Part 1 - 8 mg/kg | Part 1 - 16 mg/kg | Part 1 - 24 mg/kg | Part 2 - 8 mg/kg | Part 2 - 16 mg/kg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 7/20 (35%) | 0/3 (0%) | 1/3 (33.3%) | 2/3 (66.7%) | 2/3 (66.7%) | 12/30 (40%) | 16/42 (38.1%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Neutropenia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Thrombocytopenia | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Cardiac disorders | ||||||||||||||
| Atrial Fibrillation | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Atrial Flutter | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal Pain | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Nausea | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| General disorders | ||||||||||||||
| Chest Pain | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Oedema Peripheral | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Pyrexia | 1/20 (5%) | 0/3 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 1/30 (3.3%) | 2/42 (4.8%) | |||||||
| Hepatobiliary disorders | ||||||||||||||
| Hepatic Function Abnormal | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Immune system disorders | ||||||||||||||
| Cytokine Release Syndrome | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Bacteraemia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Bacterial Sepsis | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Herpes Zoster | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 2/42 (4.8%) | |||||||
| Influenza | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Metapneumovirus Infection | 0/20 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Pneumonia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 3/30 (10%) | 3/42 (7.1%) | |||||||
| Respiratory Syncytial Virus Infection | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Urinary Tract Infection | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Varicella | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Injury, poisoning and procedural complications | ||||||||||||||
| Limb Traumatic Amputation | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Spinal Compression Fracture | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Investigations | ||||||||||||||
| Blood Creatinine Increased | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Crossmatch Incompatible | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 3/42 (7.1%) | |||||||
| Free Haemoglobin Present | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| International Normalised Ratio Increased | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Hypokalaemia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Hypomagnesaemia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Back Pain | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Bone Pain | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Osteoporotic Fracture | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Plasmacytoma | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Nervous system disorders | ||||||||||||||
| Amnesia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Transient Ischaemic Attack | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Vith Nerve Paralysis | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Confusional State | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Bronchospasm | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/30 (0%) | 0/42 (0%) | |||||||
Other (Not Including Serious) Adverse Events |
||||||||||||||
| Part 1 - <4 mg/kg | Part 1 - 4 mg/kg | Part 1 - 8 mg/kg | Part 1 - 16 mg/kg | Part 1 - 24 mg/kg | Part 2 - 8 mg/kg | Part 2 - 16 mg/kg | ||||||||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/20 (95%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 3/3 (100%) | 30/30 (100%) | 41/42 (97.6%) | |||||||
| Blood and lymphatic system disorders | ||||||||||||||
| Anaemia | 4/20 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 3/42 (7.1%) | |||||||
| Haemolysis | 3/20 (15%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Leukopenia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 4/42 (9.5%) | |||||||
| Lymphopenia | 2/20 (10%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Monocytopenia | 2/20 (10%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Neutropenia | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 4/42 (9.5%) | |||||||
| Thrombocytopenia | 3/20 (15%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 3/42 (7.1%) | |||||||
| Cardiac disorders | ||||||||||||||
| Palpitations | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Supraventricular Extrasystoles | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Tachycardia | 2/20 (10%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Eye disorders | ||||||||||||||
| Ocular Hyperaemia | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Vision Blurred | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 5/42 (11.9%) | |||||||
| Gastrointestinal disorders | ||||||||||||||
| Abdominal Pain | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Aphthous Stomatitis | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 0/42 (0%) | |||||||
| Constipation | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 4/30 (13.3%) | 4/42 (9.5%) | |||||||
| Diarrhoea | 1/20 (5%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 9/30 (30%) | 6/42 (14.3%) | |||||||
| Dry Mouth | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Dyspepsia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 1/42 (2.4%) | |||||||
| Lip Oedema | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Mouth Ulceration | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Nausea | 2/20 (10%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 4/30 (13.3%) | 10/42 (23.8%) | |||||||
| Oesophagitis | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Stomatitis | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 1/42 (2.4%) | |||||||
| Vomiting | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 5/30 (16.7%) | 2/42 (4.8%) | |||||||
| General disorders | ||||||||||||||
| Chest Discomfort | 0/20 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 1/42 (2.4%) | |||||||
| Chest Pain | 2/20 (10%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 5/42 (11.9%) | |||||||
| Chills | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 5/42 (11.9%) | |||||||
| Fatigue | 2/20 (10%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 13/30 (43.3%) | 19/42 (45.2%) | |||||||
| Influenza Like Illness | 3/20 (15%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/30 (3.3%) | 1/42 (2.4%) | |||||||
| Oedema Peripheral | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 1/42 (2.4%) | |||||||
| Pyrexia | 7/20 (35%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 12/30 (40%) | 9/42 (21.4%) | |||||||
| Hepatobiliary disorders | ||||||||||||||
| Hepatic Function Abnormal | 0/20 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Immune system disorders | ||||||||||||||
| Cytokine Release Syndrome | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Hypersensitivity | 1/20 (5%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Infections and infestations | ||||||||||||||
| Gastroenteritis | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Herpes Zoster | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 4/30 (13.3%) | 2/42 (4.8%) | |||||||
| Nasopharyngitis | 2/20 (10%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 7/30 (23.3%) | 16/42 (38.1%) | |||||||
| Oral Candidiasis | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 1/42 (2.4%) | |||||||
| Pneumonia | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 1/42 (2.4%) | |||||||
| Sinusitis | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 4/42 (9.5%) | |||||||
| Upper Respiratory Tract Infection | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 8/30 (26.7%) | 11/42 (26.2%) | |||||||
| Urinary Tract Infection | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 2/42 (4.8%) | |||||||
| Viral Infection | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Vulvovaginal Candidiasis | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Investigations | ||||||||||||||
| Blood Creatine Phosphokinase Increased | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 2/42 (4.8%) | |||||||
| Electrocardiogram QT Prolonged | 5/20 (25%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Free Haemoglobin Present | 4/20 (20%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Haptoglobin Decreased | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Lymphocyte Count Decreased | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Metabolism and nutrition disorders | ||||||||||||||
| Decreased Appetite | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 4/42 (9.5%) | |||||||
| Enzyme Abnormality | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Hypercalcaemia | 0/20 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Hyperglycaemia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 5/42 (11.9%) | |||||||
| Hyponatraemia | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Musculoskeletal and connective tissue disorders | ||||||||||||||
| Arthralgia | 2/20 (10%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 4/30 (13.3%) | 8/42 (19%) | |||||||
| Back Pain | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 3/30 (10%) | 14/42 (33.3%) | |||||||
| Bone Pain | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 6/30 (20%) | 4/42 (9.5%) | |||||||
| Kyphosis | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Musculoskeletal Chest Pain | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 4/42 (9.5%) | |||||||
| Musculoskeletal Pain | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 4/42 (9.5%) | |||||||
| Myalgia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 6/30 (20%) | 1/42 (2.4%) | |||||||
| Pain in Extremity | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 6/42 (14.3%) | |||||||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||||||||||||
| Basal Cell Carcinoma | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 3/42 (7.1%) | |||||||
| Benign Neoplasm of Skin | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Nervous system disorders | ||||||||||||||
| Dizziness | 3/20 (15%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 5/30 (16.7%) | 4/42 (9.5%) | |||||||
| Dysgeusia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 0/42 (0%) | |||||||
| Headache | 1/20 (5%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 4/42 (9.5%) | |||||||
| Hypoaesthesia | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 2/42 (4.8%) | |||||||
| Paraesthesia | 0/20 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Peripheral Sensory Neuropathy | 0/20 (0%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 5/30 (16.7%) | 1/42 (2.4%) | |||||||
| Psychiatric disorders | ||||||||||||||
| Confusional State | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Insomnia | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 4/30 (13.3%) | 5/42 (11.9%) | |||||||
| Renal and urinary disorders | ||||||||||||||
| Pollakiuria | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Proteinuria | 9/20 (45%) | 1/3 (33.3%) | 3/3 (100%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Renal Impairment | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Reproductive system and breast disorders | ||||||||||||||
| Prostatitis | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Respiratory, thoracic and mediastinal disorders | ||||||||||||||
| Bronchospasm | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 1/30 (3.3%) | 0/42 (0%) | |||||||
| Cough | 4/20 (20%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 6/30 (20%) | 11/42 (26.2%) | |||||||
| Dysphonia | 0/20 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Dyspnoea | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 8/30 (26.7%) | 7/42 (16.7%) | |||||||
| Epistaxis | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 0/42 (0%) | |||||||
| Laryngitis Allergic | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 1/42 (2.4%) | |||||||
| Nasal Congestion | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 4/30 (13.3%) | 7/42 (16.7%) | |||||||
| Oropharyngeal Pain | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 5/42 (11.9%) | |||||||
| Productive Cough | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 0/42 (0%) | |||||||
| Rhinitis Allergic | 1/20 (5%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 12/30 (40%) | 10/42 (23.8%) | |||||||
| Throat Irritation | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 3/42 (7.1%) | |||||||
| Throat Tightness | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 3/42 (7.1%) | |||||||
| Skin and subcutaneous tissue disorders | ||||||||||||||
| Eczema Asteatotic | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
| Erythema | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 1/42 (2.4%) | |||||||
| Hyperhidrosis | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 3/30 (10%) | 2/42 (4.8%) | |||||||
| Pruritus | 0/20 (0%) | 1/3 (33.3%) | 0/3 (0%) | 1/3 (33.3%) | 0/3 (0%) | 2/30 (6.7%) | 1/42 (2.4%) | |||||||
| Rash | 1/20 (5%) | 1/3 (33.3%) | 1/3 (33.3%) | 0/3 (0%) | 0/3 (0%) | 4/30 (13.3%) | 2/42 (4.8%) | |||||||
| Vascular disorders | ||||||||||||||
| Flushing | 2/20 (10%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 1/30 (3.3%) | 1/42 (2.4%) | |||||||
| Hot Flush | 0/20 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 2/30 (6.7%) | 1/42 (2.4%) | |||||||
| Hypertension | 2/20 (10%) | 0/3 (0%) | 2/3 (66.7%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 3/42 (7.1%) | |||||||
| Hypotension | 2/20 (10%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/3 (0%) | 0/30 (0%) | 0/42 (0%) | |||||||
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
If an investigator wishes to publish information from the study, a copy of the manuscript must be provided to the sponsor for review at least 60 days before submission for publication or presentation. If requested by the sponsor in writing, the investigator will withhold such publication for up to an additional 60 days.
Results Point of Contact
| Name/Title | Senior Director |
|---|---|
| Organization | Janssen Research & Development, LLC |
| Phone | |
| ClinicalTrialDisclosure@its.jnj.com |
Responsible Party:
Janssen Research & Development, LLC
ClinicalTrials.gov Identifier:
NCT00574288
Other Study ID Numbers:
- CR101876
- GEN501
- DARA-GEN501
- 2007-003783-22
First Posted:
Dec 17, 2007
Last Update Posted:
Apr 27, 2018
Last Verified:
Mar 1, 2018