Trial Outcomes & Findings for Study of Vorinostat (MK-0683) With Follicular Lymphoma (FL), Other Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL), or Mantle Cell Lymphoma (MCL) Participants (MK-0683-103) (NCT NCT00875056)

Last Updated: 2020-10-29

Results Overview

ORR was defined as the percentage of participants who had a Complete Response (CR: Normal liver/spleen physical exam, all lymph nodes and nodal masses are normal, and there is no bone marrow involvement), a Complete Response/unconfirmed (CRu: Normal liver/spleen physical exam, plus at least a 75% decrease in the sum of the products of the greatest diameters of nodal masses if any are greater than 1.5 cm in their greatest diameter, normal or indeterminate bone marrow involvement), or a Partial Response (PR: Either normal physical exam, lymph nodes, and lymph node masses plus positive bone marrow involvement; OR normal physical exam or decrease in liver/spleen size plus at least a 50% decrease in the diameters of lymph nodes and nodal masses) as assessed using the international working group Non-Hodgkin's lymphoma standardized response criteria described by Cheson, BD in 1999. The percentage of participants who experienced a CR, CRu, or PR is presented.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

56 participants

Primary outcome timeframe

Up to 650 days

Results posted on

2020-10-29

Participant Flow

Participant milestones

Participant milestones
Measure	Follicular Lymphoma (FL) Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Overall Study STARTED	39	11	6
Overall Study COMPLETED	16	2	0
Overall Study NOT COMPLETED	23	9	6

Reasons for withdrawal

Reasons for withdrawal
Measure	Follicular Lymphoma (FL) Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Overall Study Adverse Event	6	1	2
Overall Study Progressive Disease	14	8	3
Overall Study Withdrawal by Subject	3	0	1

Baseline Characteristics

Study of Vorinostat (MK-0683) With Follicular Lymphoma (FL), Other Indolent B-cell Non-Hodgkin's Lymphoma (B-NHL), or Mantle Cell Lymphoma (MCL) Participants (MK-0683-103)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Follicular Lymphoma (FL) n=39 Participants Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL n=11 Participants Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease n=6 Participants Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.	Total n=56 Participants Total of all reporting groups
Age, Continuous	57.4 Years STANDARD_DEVIATION 10.4 • n=5 Participants	62.9 Years STANDARD_DEVIATION 9.7 • n=7 Participants	56.3 Years STANDARD_DEVIATION 10.5 • n=5 Participants	58.4 Years STANDARD_DEVIATION 10.4 • n=4 Participants
Sex: Female, Male Female	24 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	30 Participants n=4 Participants
Sex: Female, Male Male	15 Participants n=5 Participants	7 Participants n=7 Participants	4 Participants n=5 Participants	26 Participants n=4 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	39 Participants n=5 Participants	11 Participants n=7 Participants	6 Participants n=5 Participants	56 Participants n=4 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Asian	39 Participants n=5 Participants	11 Participants n=7 Participants	6 Participants n=5 Participants	56 Participants n=4 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants

PRIMARY outcome

Timeframe: Up to 650 days

Population: The analysis population included all allocated participants with follicular lymphoma (FL), non-FL B cell non-Hodgkin's lymphoma (B-NHL), or mantle cell lymphoma (MCL) who received at least one dose of study drug, and had some post-allocation endpoint data.

Outcome measures

Outcome measures
Measure	Follicular Lymphoma (FL) n=39 Participants Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL n=11 Participants Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Objective Response Rate (ORR)	48.7 Percentage of participants Interval 32.4 to 65.2	27.3 Percentage of participants Interval 6.0 to 61.0	—

PRIMARY outcome

Timeframe: Up to approximately 29 months

Population: All allocated participants who received a dose of study drug were included in this analysis.

An AE was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who experienced an AE was presented.

Outcome measures

Outcome measures
Measure	Follicular Lymphoma (FL) n=39 Participants Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL n=11 Participants Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease n=6 Participants Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Number of Participants Who Experienced an Adverse Event (AE)	39 Participants	11 Participants	6 Participants

PRIMARY outcome

Timeframe: Up to 536 days

Population: All allocated participants who received a dose of study drug were included in this analysis.

An adverse event (AE) was defined as any untoward medical occurrence in a participant administered study treatment and which did not necessarily have to have a causal relationship with this treatment. The number of participants who discontinued from study drug due to an adverse event was reported.

Outcome measures

Outcome measures
Measure	Follicular Lymphoma (FL) n=39 Participants Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL n=11 Participants Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease n=6 Participants Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Number of Participants Who Discontinued Study Drug Due to Experiencing an Adverse Event (AE)	6 Participants	1 Participants	2 Participants

SECONDARY outcome

Timeframe: Up to 650 days

Population: The analysis population included all allocated participants with FL who received at least one dose of study drug, and had some post-allocation endpoint data.

Time to Treatment Failure is defined as the time from allocation until the date of any treatment failure, including documented disease progression, or discontinuation of the study medication for any reason. Data was censored on the efficacy data cutoff date of 25 February, 2011.

Outcome measures

Outcome measures
Measure	Follicular Lymphoma (FL) n=39 Participants Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Time to Treatment Failure for Relapsed/Refractory FL	323 Days Interval 60.0 to For time to treatment failure upper limit, not all participants had experienced a response by the time of efficacy data cutoff, making the data not available.	—	—

SECONDARY outcome

Timeframe: Up to 650 days

Population: The analysis population included all allocated participants with FL who received at least one dose of study drug, and had some post-allocation endpoint data.

Time to Response is defined as the time from allocation until the time of an initial response. Data was censored on the efficacy data cutoff date of 25 February, 2011.

Outcome measures

Outcome measures
Measure	Follicular Lymphoma (FL) n=39 Participants Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Time to Response for Relapsed/Refractory FL	NA Days Median time to response not reached. For upper and lower limits, not all participants had experienced a response by the time of efficacy data cutoff, making the data not available.	—	—

Adverse Events

Follicular Lymphoma (FL)

Serious events: 9 serious events

Other events: 39 other events

Deaths: 4 deaths

Indolent Non-FL B-NHL or MCL

Serious events: 3 serious events

Other events: 11 other events

Deaths: 3 deaths

Other Disease

Serious events: 2 serious events

Other events: 6 other events

Deaths: 2 deaths

Serious adverse events

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp.

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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. Sponsor review can be expedited to meet publication guidelines.
Publication restrictions are in place

Restriction type: OTHER

Measure	Follicular Lymphoma (FL) n=39 participants at risk Participants with relapsed/refractory FL received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Indolent Non-FL B-NHL or MCL n=11 participants at risk Participants with indolent non-follicular lymphoma (FL) B-cell non-Hodgkin's lymphoma (B-NHL), or with mantle cell Lymphoma (MCL) received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol.	Other Disease n=6 participants at risk Participants with disease other than relapsed/refractory follicular lymphoma (FL), non-FL B-cell non-Hodgkin's lymphoma (B-NHL), or mantle cell Lymphoma (MCL), as assessed by the Independent Central Pathological Committee, received 200 mg of vorinostat (MK-0683) twice daily (200 mg x 2/day) for 14 consecutive days followed by 1 week (7 days) rest in a 21-day cycle, until they met the per-participant discontinuation criteria specified by the protocol. This group was created to include participants who enrolled, but whose later diagnoses by the Independent Central Pathological Committee excluded them from analysis in the FL and non-FL B-NHL/MCL groups because they had different disease than those prespecified in the protocol.
Blood and lymphatic system disorders Neutropenia	0.00% 0/39 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	9.1% 1/11 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Blood and lymphatic system disorders Thrombocytopenia	5.1% 2/39 • Number of events 2 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	9.1% 1/11 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Gastrointestinal disorders Abdominal pain	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
General disorders Asthenia	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Infections and infestations H1N1 influenza	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Infections and infestations Meningitis aseptic	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Infections and infestations Pneumonia	0.00% 0/39 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	9.1% 1/11 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Injury, poisoning and procedural complications Muscle injury	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Metabolism and nutrition disorders Decreased appetite	5.1% 2/39 • Number of events 2 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Breast cancer	0.00% 0/39 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	16.7% 1/6 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Nervous system disorders Dizziness	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Nervous system disorders VIth nerve paralysis	0.00% 0/39 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	16.7% 1/6 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pleural effusion	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Respiratory, thoracic and mediastinal disorders Pleural haemorrhage	0.00% 0/39 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	9.1% 1/11 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Vascular disorders Deep vein thrombosis	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.
Vascular disorders Embolism venous	2.6% 1/39 • Number of events 1 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/11 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.	0.00% 0/6 • Up to approximately 29 months Non-serious adverse events and serious adverse events were counted starting at the time of a participant's first treatment and included all treated participants. All-Cause Mortality was counted starting from the time of a participant's enrollment and included all randomized participants.