Trial Outcomes & Findings for Study of Ramucirumab in Ovarian Cancer (NCT NCT00721162)

NCT ID: NCT00721162

Last Updated: 2019-09-26

Results Overview

Objective response is confirmed complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion. ORR is calculated as a total number of participants with CR or PR from the start of study treatment until disease progression/recurrence or the start of new therapeutic anticancer treatment, whichever occurred first, divided by the total number of participants treated, then multiplied by 100.

• Recruitment status: COMPLETED
• Study phase: PHASE2
• Target enrollment: 60 participants
• Primary outcome timeframe: First dose to date of objective progressive disease /death or new anti-cancer therapy up to 34.6 months
• Results posted on: 2019-09-26

Participant Flow

73 participants signed informed consent.

Participant milestones

Measure	Ramucirumab Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Overall Study STARTED	60
Overall Study Received Any Amount of Study Drug	60
Overall Study COMPLETED	60
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study of Ramucirumab in Ovarian Cancer

Baseline characteristics by cohort

Measure	Ramucirumab n=60 Participants Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	36 Participants n=5 Participants
Age, Categorical >=65 years	24 Participants n=5 Participants
Sex: Female, Male Female	60 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	59 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race/Ethnicity, Customized Black or African American	5 participants n=5 Participants
Race/Ethnicity, Customized White	52 participants n=5 Participants
Race/Ethnicity, Customized Other	3 participants n=5 Participants
Region of Enrollment United States	56 participants n=5 Participants
Region of Enrollment United Kingdom	4 participants n=5 Participants

PRIMARY outcome

Timeframe: First Dose to 6 Months

Population: All participants who received any amount of study drug.

Data presented are the percentage of participants without progressive disease (PD) or death from any cause at 6 month after first dose. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or new lesion.

Outcome measures

Measure	Ramucirumab n=60 Participants Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Percentage of Participants With Progression-Free Survival at 6 Months (PFS-6)	25.0 percentage of participants Interval 14.7 to 37.9

PRIMARY outcome

Timeframe: First dose to date of objective progressive disease /death or new anti-cancer therapy up to 34.6 months

Population: All participants who received any amount of study drug.

Objective response is confirmed complete response (CR) + partial response (PR), as classified by the investigators according to the Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. CR is disappearance of all target and non-target lesions; PR is ≥30% decrease in sum of longest diameter of target lesions without new lesion and progression of non-target lesion. ORR is calculated as a total number of participants with CR or PR from the start of study treatment until disease progression/recurrence or the start of new therapeutic anticancer treatment, whichever occurred first, divided by the total number of participants treated, then multiplied by 100.

Outcome measures

Measure	Ramucirumab n=60 Participants Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Objective Response Rate (ORR): Percentage of Participants With Complete Response (CR) and Partial Response (PR)	5.0 percentage of participants Interval 1.0 to 13.9

SECONDARY outcome

Timeframe: First dose to measured progressive disease or death due to any cause up to 34.6 months

Population: All participants who received any amount of study drug. The number of participants censored was 11.

Defined as the time from date of first dose to the first observation of progression of disease (PD) or death due to any cause. PD was determined using Response Evaluation Criteria In Solid Tumors (RECIST) criteria version 1.0. PD is ≥20% increase in sum of longest diameter of target lesions and/or unequivocal progression of non-target lesion and/or new lesion. For participants who had no PD or death or had started new therapeutic anticancer treatment, PFS was censored at their last radiographic tumor assessment.

Outcome measures

Measure	Ramucirumab n=60 Participants Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Progression-Free Survival (PFS)	3.5 months Interval 2.3 to 5.3

SECONDARY outcome

Timeframe: First dose to 12 months

Population: All participants who received any amount of study drug.

Data presented are the percentage of participants surviving at least 12 months after first dose based on Kaplan Meier Method.

Outcome measures

Measure	Ramucirumab n=60 Participants Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Overall Survival at 1 Year (OS-1)	48.0 percentage of participants Interval 34.9 to 59.9

SECONDARY outcome

Timeframe: First dose to death due to any cause up to 43.9 months

Population: All participants who received any amount of study drug. The number of participants censored was 12.

Overall survival is defined as the time from first dose to the date of death due to any cause. For participants who were alive or were lost to follow-up, overall survival was censored on the last date the participant was known to be alive.

Outcome measures

Measure	Ramucirumab n=60 Participants Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Overall Survival (OS)	11.1 months Interval 8.3 to 17.0

SECONDARY outcome

Timeframe: First dose to 30 months

Population: All participants who received any amount of study drug.

Data presented are the number of participants who experienced treatment-emergent adverse events (TEAE), serious adverse events (SAE), Grade 3 or 4 TEAE, or adverse events (AE) leading to discontinuation of treatment that were considered to be related to ramucirumab. A summary of SAEs and other nonserious AEs, regardless of causality, is located in the Reported Adverse Events section.

Outcome measures

Measure	Ramucirumab n=60 Participants Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events Related SAE	10 participants
Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events Related TEAE	56 participants
Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events Related Grade 3 or 4 TEAE	21 participants
Summary Listing of Participants Reporting Drug-Related Treatment-Emergent Adverse Events Related AE leading to discontinuation	4 participants

Adverse Events

Ramucirumab

Serious events: 22 serious events

Other events: 58 other events

Deaths: 0 deaths

Serious adverse events

Measure	Ramucirumab n=60 participants at risk Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Blood and lymphatic system disorders Thrombocytopenia	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Cardiac disorders Mitral valve incompetence	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Ascites	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Gastritis	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Intestinal perforation	3.3% 2/60 • Number of events 3 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Nausea	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Rectal haemorrhage	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Small intestinal obstruction	5.0% 3/60 • Number of events 5 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Vomiting	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
General disorders Abscess sterile	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
General disorders Hernia obstructive	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
General disorders Oedema peripheral	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
General disorders Pyrexia	1.7% 1/60 • Number of events 2 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Infections and infestations Peritonitis	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Infections and infestations Postoperative wound infection	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Infections and infestations Sepsis	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Injury, poisoning and procedural complications Expired drug administered	5.0% 3/60 • Number of events 3 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Investigations Alanine aminotransferase increased	3.3% 2/60 • Number of events 2 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Investigations Aspartate aminotransferase increased	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Investigations Hepatic enzyme increased	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Metabolism and nutrition disorders Hypercalcaemia	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Metabolism and nutrition disorders Hypokalaemia	1.7% 1/60 • Number of events 2 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Neoplasm progression	6.7% 4/60 • Number of events 5 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Nervous system disorders Neuralgia	1.7% 1/60 • Number of events 2 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Renal and urinary disorders Renal failure acute	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Reproductive system and breast disorders Female genital tract fistula	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Respiratory, thoracic and mediastinal disorders Dyspnoea	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Respiratory, thoracic and mediastinal disorders Pleural effusion	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Vascular disorders Deep vein thrombosis	1.7% 1/60 • Number of events 1 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.

Other adverse events

Measure	Ramucirumab n=60 participants at risk Ramucirumab at 8 milligrams/kilogram (mg/kg) administered intravenously over 1 hour every other week (every 14 days) of a 28-day cycle.
Musculoskeletal and connective tissue disorders Myalgia	11.7% 7/60 • Number of events 9 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Musculoskeletal and connective tissue disorders Pain in extremity	13.3% 8/60 • Number of events 11 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Nervous system disorders Dizziness	11.7% 7/60 • Number of events 8 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Nervous system disorders Dysgeusia	6.7% 4/60 • Number of events 4 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Nervous system disorders Headache	71.7% 43/60 • Number of events 72 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Psychiatric disorders Insomnia	11.7% 7/60 • Number of events 7 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Blood and lymphatic system disorders Anaemia	18.3% 11/60 • Number of events 21 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Blood and lymphatic system disorders Thrombocytopenia	10.0% 6/60 • Number of events 20 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Abdominal discomfort	6.7% 4/60 • Number of events 4 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Abdominal distension	11.7% 7/60 • Number of events 7 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Abdominal pain	20.0% 12/60 • Number of events 14 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Abdominal pain lower	8.3% 5/60 • Number of events 5 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Constipation	21.7% 13/60 • Number of events 15 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Diarrhoea	35.0% 21/60 • Number of events 41 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Dyspepsia	10.0% 6/60 • Number of events 8 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Gastrooesophageal reflux disease	6.7% 4/60 • Number of events 4 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Gingival bleeding	10.0% 6/60 • Number of events 10 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Nausea	43.3% 26/60 • Number of events 38 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Stomatitis	18.3% 11/60 • Number of events 15 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Gastrointestinal disorders Vomiting	33.3% 20/60 • Number of events 31 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
General disorders Chills	8.3% 5/60 • Number of events 8 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
General disorders Fatigue	68.3% 41/60 • Number of events 72 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
General disorders Oedema peripheral	26.7% 16/60 • Number of events 23 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
General disorders Pyrexia	13.3% 8/60 • Number of events 11 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Infections and infestations Nasopharyngitis	6.7% 4/60 • Number of events 6 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Infections and infestations Sinusitis	6.7% 4/60 • Number of events 4 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Infections and infestations Upper respiratory tract infection	6.7% 4/60 • Number of events 5 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Infections and infestations Urinary tract infection	21.7% 13/60 • Number of events 19 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Investigations Alanine aminotransferase increased	6.7% 4/60 • Number of events 7 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Investigations Aspartate aminotransferase increased	6.7% 4/60 • Number of events 11 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Investigations Weight decreased	15.0% 9/60 • Number of events 13 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Metabolism and nutrition disorders Decreased appetite	20.0% 12/60 • Number of events 16 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Metabolism and nutrition disorders Hyperglycaemia	11.7% 7/60 • Number of events 8 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Metabolism and nutrition disorders Hypoalbuminaemia	8.3% 5/60 • Number of events 5 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Metabolism and nutrition disorders Hypomagnesaemia	10.0% 6/60 • Number of events 6 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Musculoskeletal and connective tissue disorders Arthralgia	20.0% 12/60 • Number of events 18 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Musculoskeletal and connective tissue disorders Back pain	15.0% 9/60 • Number of events 13 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Musculoskeletal and connective tissue disorders Joint swelling	10.0% 6/60 • Number of events 7 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Musculoskeletal and connective tissue disorders Muscular weakness	6.7% 4/60 • Number of events 4 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Renal and urinary disorders Proteinuria	13.3% 8/60 • Number of events 10 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Reproductive system and breast disorders Vaginal haemorrhage	6.7% 4/60 • Number of events 6 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Respiratory, thoracic and mediastinal disorders Cough	21.7% 13/60 • Number of events 14 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Respiratory, thoracic and mediastinal disorders Dysphonia	10.0% 6/60 • Number of events 7 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Respiratory, thoracic and mediastinal disorders Dyspnoea	20.0% 12/60 • Number of events 15 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Respiratory, thoracic and mediastinal disorders Epistaxis	13.3% 8/60 • Number of events 15 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	8.3% 5/60 • Number of events 5 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Skin and subcutaneous tissue disorders Alopecia	8.3% 5/60 • Number of events 5 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Skin and subcutaneous tissue disorders Pruritus	6.7% 4/60 • Number of events 4 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Vascular disorders Flushing	8.3% 5/60 • Number of events 6 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.
Vascular disorders Hypertension	26.7% 16/60 • Number of events 19 Deaths due to progressive disease are not considered adverse events (AE). Four deaths due to progressive disease were recorded by the investigator as serious AEs (SAE) and are captured in the SAE summary.

Additional Information

Chief Medical Officer

Eli Lilly and Company

Phone: 800-545-5979

Results disclosure agreements

• Principal investigator is a sponsor employee Investigators agreed to delay independently publishing or disclosing data, findings or conclusions from the study except as part of a multi-center publication. Upon study publication or if the draft publication is not produced within approximately 6 months of the final report of the study results, investigators may independently publish, subject to confidential information review/redaction by sponsor. The sponsor may request publication delay up to 90 days to seek patent protection.
• Publication restrictions are in place

Restriction type: OTHER