Trial Outcomes & Findings for Genistein Supplementation to Mitigate Cardiometabolic Dysfunction in Patients Undergoing Androgen Deprivation Therapy for Prostate Cancer (NCT NCT02766478)

Last Updated: 2022-09-27

Results Overview

The Matsuda index is a measurement of insulin sensitivity from plasma glucose and insulin concentrations during the oral glucose tolerance test (OGTT). Insulin sensitivity was calculated at baseline and after 8 weeks with Matsuda index \[10,000 / √glucose 0' x insulin 0') (mean glucose oral glucose tolerance test (OGTT) x mean insulin OGTT)\]. Higher values are reflective of better insulin sensitivity. This test is not used to clinically diagnose disease, and there is no accepted, standard cutoff to define impaired insulin sensitivity or insulin resistance based on this index.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

10 participants

Primary outcome timeframe

Baseline, Week 8 post-baseline

Results posted on

2022-09-27

Participant Flow

Participants were enrolled between October 2017 and March 2021. 10 participants consented to take part in the study and 2 withdrew at some point in the study. Results are presented on all data provided by all participants before withdrawal, where applicable.

Participant milestones

Participant milestones
Measure	Genistein Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily). Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily). Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Placebo Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.
Overall Study STARTED	6	4
Overall Study COMPLETED	5	3
Overall Study NOT COMPLETED	1	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Genistein Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily). Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily). Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Placebo Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.
Overall Study Withdrawal by Subject	1	1

Baseline Characteristics

Genistein Supplementation to Mitigate Cardiometabolic Dysfunction in Patients Undergoing Androgen Deprivation Therapy for Prostate Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Genistein n=6 Participants Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily). Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily). Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Placebo n=4 Participants Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Total n=10 Participants Total of all reporting groups
Age, Continuous	69.5 years n=5 Participants	67.5 years n=7 Participants	69.5 years n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Male	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	6 Participants n=5 Participants	4 Participants n=7 Participants	10 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 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
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) White	5 Participants n=5 Participants	2 Participants n=7 Participants	7 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	6 participants n=5 Participants	4 participants n=7 Participants	10 participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline, Week 8 post-baseline

Population: Number of patients included only subjects that were able to complete the outcome assessment in each visit.

Outcome measures

Outcome measures
Measure	Genistein n=6 Participants Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily). Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily). Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Placebo n=3 Participants Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.
Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline Baseline	4.4 index Interval 2.4 to 5.5	6.1 index Interval 3.9 to 13.5
Matsuda Index of Whole-Body Insulin Sensitivity at Baseline and Week 8 Post-baseline 8 weeks post-baseline	4.1 index Interval 2.1 to 4.4	7.7 index Interval 5.0 to 10.3

PRIMARY outcome

Timeframe: Baseline, Week 8 post-baseline

Population: Number of patients included only subjects that were able to complete the outcome assessment in each visit.

β-cell insulin secretion was determined from the OGTT. It is calculated as the ratio of the change in insulin values over the first 30 minutes of the OGTT and the change in glucose values over the first 30 minutes. Higher values are reflective of higher insulin secretion. This test is not used to clinically diagnose disease, and there is no accepted, standard cutoff to define impaired insulin secretion based on this index.

Outcome measures

Outcome measures
Measure	Genistein n=6 Participants Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily). Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily). Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Placebo n=3 Participants Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.
β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline Baseline	1.1 index Interval 0.5 to 3.3	0.7 index Interval 0.5 to 1.3
β-cell Insulin Secretion Capacity Assessed by the Insulinogenic Index at Baseline and Week 8 Post-baseline Week 8 post-baseline	2.1 index Interval 0.7 to 2.5	1.4 index Interval 1.4 to 1.4

SECONDARY outcome

Timeframe: Baseline, Week 8

Population: Number of patients included only subjects that were able to complete the outcome assessment in each visit.

Arterial stiffness will be assessed by applanation tonometry. Results will be reported in m/s (meters/seconds). A higher value indicates a worse outcome.

Outcome measures

Outcome measures
Measure	Genistein n=6 Participants Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily). Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily). Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Placebo n=3 Participants Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.
Arterial Stiffness Baseline	7.4 m/s Interval 6.1 to 9.2	7.2 m/s Interval 7.1 to 8.5
Arterial Stiffness Week 8	9.1 m/s Interval 7.9 to 9.5	7.2 m/s Interval 6.0 to 8.6

SECONDARY outcome

Timeframe: Baseline, Week 8 post-baseline

Population: Number of patients included only subjects that were able to complete the outcome assessment in each visit.

Vascular endothelial function was measured with flow-mediated dilation (FMD in %) via ultrasound. A lower FMD indicates a worse outcome.

Outcome measures

Outcome measures
Measure	Genistein n=6 Participants Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily). Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily). Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Placebo n=4 Participants Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.
Vascular Endothelial Function at Baseline and Week 8 Post-baseline Baseline	4.9 percentage of FMD Interval 3.4 to 5.2	4.7 percentage of FMD Interval 2.4 to 6.3
Vascular Endothelial Function at Baseline and Week 8 Post-baseline Week 8 post-baseline	4.4 percentage of FMD Interval 2.0 to 6.6	2.7 percentage of FMD Interval 1.1 to 8.4

Adverse Events

Genistein

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Dr. Jessica Alvarez

Emory University

Phone: 404-727-1390

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Other adverse events
Measure	Genistein n=6 participants at risk Participants with and without diabetes received 60 mg/day oral genistein (30 mg taken twice daily). Genistein: Genistein is a natural supplement that comes from soy. Genistein was taken orally (30 mg twice daily). Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.	Placebo n=4 participants at risk Participants with and without diabetes received placebo taken twice daily. Placebo: A placebo pill was taken orally. Treatment was intended for 12 weeks but due to study termination treatment only lasted up to 8 weeks.
Infections and infestations Flu	16.7% 1/6 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	0.00% 0/4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Injury, poisoning and procedural complications Fall	16.7% 1/6 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	0.00% 0/4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
General disorders Localized edema in feet and ankles	16.7% 1/6 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	0.00% 0/4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Respiratory, thoracic and mediastinal disorders Sinus congestion	16.7% 1/6 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	0.00% 0/4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Vascular disorders Hot flashes	16.7% 1/6 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	0.00% 0/4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
General disorders Dizziness	16.7% 1/6 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	0.00% 0/4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
General disorders Heat strokes	16.7% 1/6 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	0.00% 0/4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
General disorders Swollen ankles	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 2 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Surgical and medical procedures Oral surgery	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Musculoskeletal and connective tissue disorders Left hip soreness	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Gastrointestinal disorders Constipation	33.3% 2/6 • Number of events 4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Gastrointestinal disorders Constipation and diarrhea	16.7% 1/6 • Number of events 2 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 2 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Infections and infestations Bone infection (Osteomyelitis)	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Skin and subcutaneous tissue disorders Hyperhidrosis	16.7% 1/6 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	50.0% 2/4 • Number of events 2 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Gastrointestinal disorders Diarrhea	33.3% 2/6 • Number of events 4 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Reproductive system and breast disorders Genital edema	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Infections and infestations Urinary tract infection	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Skin and subcutaneous tissue disorders Rash - upper arm	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
General disorders Abdominal discomfort	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
Musculoskeletal and connective tissue disorders Back pain	33.3% 2/6 • Number of events 2 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
General disorders Hair loss on fingers	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
General disorders Insomnia	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.
General disorders Overheating	0.00% 0/6 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.	25.0% 1/4 • Number of events 1 • Adverse events (AEs) were monitored weekly throughout the 8 weeks that participants were enrolled in the study. AEs were defined as undesirable medical events or experiences, and classified as "expected", "unanticipated", or "serious" adverse events. Serious adverse events (SAEs) were predefined as experiences that suggest a significant hazard, such as events which: a) are fatal, b) are life-threatening, c) result in permanent disability, d) require inpatient hospitalization, or e) involve cancer, a congenital anomaly, or drug overdose.