Safety and Efficacy of BGS649 in Male Obese Subjects With Hypogonadotropic Hypogonadism

• Sponsor: Mereo BioPharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02730169
• Collaborator: (none)
• Enrollment: 271
• Locations: 63
• Arms: 4
• Actual Duration (Months): 24.2
• Patients Per Site: 4.3
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the safety and efficacy of BGS649 in male obese subjects with hypogonadotropic hypogonadism. All subjects will be treated for a maximum of 24 weeks. Some subjects who complete 24 weeks of treatment will be invited to participate in a 6-month blinded safety extension study (Protocol MBGS206). The study is planned to enroll 268 subjects.

Condition or Disease	Intervention/Treatment	Phase
Hypogonadotropic Hypogonadism	Drug: BGS649; Drug: Placebo	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 271 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Phase IIb Multicentre, Double-Blind, Dose-Ranging, Randomised, Placebo-Controlled Study Evaluating Safety and Efficacy of BGS649 in Male Obese Subjects With Hypogonadotropic Hypogonadism
• Actual Study Start Date: May 12, 2016
• Actual Primary Completion Date: Feb 15, 2018
• Actual Study Completion Date: May 19, 2018

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BGS649 0.1 mg BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules)	Drug: BGS649; Capsules were taken weekly for a maximum of 24 weeks
Experimental: BGS649 0.3 mg BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules)	Drug: BGS649; Capsules were taken weekly for a maximum of 24 weeks
Experimental: BGS649 1.0 mg BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules)	Drug: BGS649; Capsules were taken weekly for a maximum of 24 weeks
Placebo Comparator: Placebo Placebo weekly (3 indistinguishable placebo capsules)	Drug: Placebo; Capsules were taken weekly for a maximum of 24 weeks

Outcome Measures

Primary Outcome Measures

1. Percentage of Patients With Normalised Testosterone After 24 Weeks of Study Treatment [24 weeks of treatment]

   Percentage of patients with normalised testosterone i.e. testosterone in the range 300-1000ng/dL after 24 weeks of study treatment. The primary objective was considered met, if greater than or equal to 75% of the participants in any arm normalised.

Secondary Outcome Measures

1. The Proportion of Subjects That Have Normalization of Total Testosterone Serum Concentrations From Baseline to Week 24 [Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks]

   Normalised total testosterone level was defined as between 300-1000 ng/dL (10.4-35 nmol/L) inclusive. Levels >1000 ng/dL were considered super-physiological outside the normal range.

2. Proportion of Subjects That Overshoot Testosterone (Total Testosterone Above 1000 ng/dL [35 Nmol/L]) From Baseline to Week 24 [Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks]

   Testosterone overshoot was defined as total testosterone above 1000 ng/dL (35 nmol/L). Samples were collected in the morning before 11 am pre dose.

3. Normalization of Total Testosterone Serum Concentrations in ≥ 90% Subjects After 24 Weeks of Treatment. [24 weeks of treatment]

   Normalized total testosterone level was defined as between 300-1000 ng/dL (10.4-35 nmol/L) inclusive. Levels >1000 ng/dL were considered super-physiological outside the normal range. This secondary outcome measure was considered to have been met for a dose if ≥ 90% of subjects in the intent-to-treat (ITT) population had normalisation of total testosterone levels at Week 24.

4. Mean (SD) Change From Baseline in Luteinizing Hormone (LH) to Week 24. [Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks]

   LH was measured at screening, baseline. The Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.

5. Mean (SD) Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 24. [Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks]

   FSH was measured at baseline, Visit 1 through 8 and follow-up. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.

6. Descriptive Summary (Geometric Mean [95% CI]) of BGS649 Plasma PK Concentration Values to 24 Weeks. [Week 12 (pre-dose and 1 hour post-dose), week 24 and week 24/End of treatment]

   Plasma PK sampling for BGS649 was performed at Weeks 12 and 24. BGS649 PK plasma concentrations were summarised for the PK population by descriptive statistics.

7. Descriptive Summary (Geometric Mean [95% CI]) of BGS649 Semen PK Concentration Values at 24 Weeks. [Week 24 and week 24/End of treatment]

   Semen PK sampling for BGS649 was performed at Visit 8 (End of Treatment). BGS649 PK semen concentrations were summarised for the PK population by descriptive statistics.

Other Outcome Measures

1. Mean (SD) Change From Baseline in Prostate Specific Antigen (PSA) to Week 24. [Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks]

   PSA was measured alongside other clinical chemistry parameters at screening, baseline, Visits 1 through 8 and at follow-up.

2. Mean (SD) Change From Baseline in Haematocrit to Week 24. [Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks]

   Haematocrit was measured alongside other haematology parameters at screening, baseline, Visits 1 through 8 and at follow-up.

3. Mean (SD) Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan T-score by Location at Week 24. [Screening to Week 24]

   Summary of DEXA Scan T-score at Visit 8 (Week 24) in the hip, femoral neck, and lumber spine. DEXA T-score was calculated based on actual measured bone density value and compared to a standard reference range for healthy young adult men.

4. Mean (SD) Change From Baseline in DEXA Scan Density by Location at Week 24 [Screening to Week 24]

   Summary of DEXA scan density at Visit 8 (Week 24) in the hip, femoral neck, and lumber spine. Bone density was evaluated with standard procedure for Hologic and General Electric Lunar scanners.

5. Mean (SD) Change From Baseline in Bone Turnover Markers by Parameter at Week 24. [Screening to Week 24]

   Descriptive statistics were presented for the following bone turnover marker parameters: type I collagen C-telopeptides, procollagen 1 N-terminal propeptide, osteocalcin, and bone specific alkaline phosphatase.

6. Change From Baseline in Bone Specific Alkaline Phosphatase at Week 24. [24 weeks]

   Change from baseline in bone specific alkaline phosphatase at week 24 measured in U/L

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: Male
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Adult male subject aged 18 to 65 years inclusive

• BMI > 30 kg/m2 and < 50 kg/m2

• Serum total testosterone concentration below the normal range

• LH levels below the upper limit of normal

• Oestradiol levels within or above the normal range of approved assay

• At least two symptoms of androgen deficiency present for at least 2 months prior to the first Screening Visit, with at least one of these being a sexual dysfunction

Exclusion Criteria:

• Evidence of clinically significant endocrinopathy at screening that may interfere with the study assessments

• Other types of hypogonadotropic hypogonadism or primary hypogonadism

• Any other pituitary or hypothalamic disease

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Mereo Research Site	Birmingham	Alabama	United States
2	Mereo Research Site	Mobile	Alabama	United States
3	Mereo Research Site	Chandler	Arizona	United States
4	Mereo Research Site	Phoenix	Arizona	United States
5	Mereo Research Site	Scottsdale	Arizona	United States
6	Mereo Research Site	Anaheim	California	United States
7	Mereo Research Site	Carlsbad	California	United States
8	Mereo Research Site	Greenbrae	California	United States
9	Mereo Research Site	Lincoln	California	United States
10	Mereo Research Site	Los Angeles	California	United States
11	Mereo Research Site	San Diego	California	United States
12	Mereo Research Site	Bradenton	Florida	United States
13	Mereo Research Site	DeLand	Florida	United States
14	Mereo Research Site	Fort Myers	Florida	United States
15	Mereo Research Site	Hialeah	Florida	United States
16	Mereo Research Site	Homestead	Florida	United States
17	Mereo Research Site	Saint Petersburg	Florida	United States
18	Mereo Research Site	Meridian	Idaho	United States
19	Mereo Research Site	Gurnee	Illinois	United States
20	Mereo Research Site	Evansville	Indiana	United States
21	Mereo Research Site	New Orleans	Louisiana	United States
22	Mereo Research Site	Baltimore	Maryland	United States
23	Mereo Research Site	Elkridge	Maryland	United States
24	Mereo Research Site	Saint Louis	Missouri	United States
25	Mereo Research Site	Omaha	Nebraska	United States
26	Mereo Research Site	Henderson	Nevada	United States
27	Mereo Research Site	Las Vegas	Nevada	United States
28	Mereo Research Site	Albany	New York	United States
29	Mereo Research Site	Garden City	New York	United States
30	Mereo Research Site	Great Neck	New York	United States
31	Mereo Research Site	New York	New York	United States
32	Mereo Research Site	Rochester	New York	United States
33	Mereo Research Site	Charlotte	North Carolina	United States
34	Mereo Research Site	Raleigh	North Carolina	United States
35	Mereo Research Site	Winston-Salem	North Carolina	United States
36	Mereo Research Site	Middleburg Heights	Ohio	United States
37	Mereo Research Site	Mount Pleasant	South Carolina	United States
38	Mereo Research Site	Nashville	Tennessee	United States
39	Mereo Research Site	Smyrna	Tennessee	United States
40	Mereo Research Site	Spring Hill	Tennessee	United States
41	Mereo Research Site	Dallas	Texas	United States
42	Mereo Research Site	Fort Worth	Texas	United States
43	Mereo Research Site	Pearland	Texas	United States
44	Mereo Research Site	San Antonio	Texas	United States
45	Mereo Research Site	Murray	Utah	United States
46	Mereo Research Site	West Jordan	Utah	United States
47	Mereo Research Site	Norfolk	Virginia	United States
48	Mereo Research Site	Kenosha	Wisconsin	United States
49	Mereo Research Site	Ancona		Italy
50	Mereo Research Site	Parma		Italy
51	Mereo Research Site	Roma		Italy
52	Mereo Research Site	Siena		Italy
53	Mereo Research Site	Coslada		Spain
54	Mereo Research Site	Girona		Spain
55	Mereo Research Site	Madrid		Spain
56	Mereo Research Site	Majadahonda		Spain
57	Mereo Research Site	Barnsley		United Kingdom
58	Mereo Research Site	Coventry		United Kingdom
59	Mereo Research Site	Dundee		United Kingdom
60	Mereo Research Site	Edinburgh		United Kingdom
61	Mereo Research Site	Hull		United Kingdom
62	Mereo Research Site	Manchester		United Kingdom
63	Mereo Research Site	Newcastle		United Kingdom

Sponsors and Collaborators

• Mereo BioPharma

Investigators

• Principal Investigator: Hugh Jones, Barnsley Hospital NHS Foundation Trust

Study Documents (Full-Text)

• Study Protocol - Mar 10, 2017
• Statistical Analysis Plan - Jun 7, 2018

More Information

Publications

None provided.

• Responsible Party: Mereo BioPharma
• ClinicalTrials.gov Identifier: NCT02730169
• Other Study ID Numbers: MBGS205
• First Posted: Apr 6, 2016
• Last Update Posted: Nov 25, 2020
• Last Verified: Nov 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mereo BioPharma: Hypogonadotropic; hypogonadism; testosterone
• Additional relevant MeSH terms: Hypogonadism

Study Results

Participant Flow

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Period Title: Overall Study
STARTED	67	66	67	71
COMPLETED	53	45	50	55
NOT COMPLETED	14	21	17	16

Baseline Characteristics

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo	Total
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks	Total of all reporting groups
Overall Participants	67	66	67	71	271
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	51.4 (8.39)	51.6 (7.31)	49.6 (9.72)	50.9 (9.17)	50.8 (8.69)
Sex: Female, Male (Count of Participants)
Female	0 0%	0 0%	0 0%	0 0%	0 0%
Male	67 100%	66 100%	67 100%	71 100%	271 100%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 1.5%	0 0%	0 0%	0 0%	1 0.4%
Asian	0 0%	2 3%	2 3%	0 0%	4 1.5%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	1 1.5%	0 0%	1 0.4%
Black or African American	12 17.9%	13 19.7%	15 22.4%	7 9.9%	47 17.3%
White	53 79.1%	49 74.2%	49 73.1%	61 85.9%	212 78.2%
More than one race	0 0%	0 0%	0 0%	0 0%	0 0%
Unknown or Not Reported	1 1.5%	2 3%	0 0%	3 4.2%	6 2.2%

Outcome Measures

1. Primary Outcome

Title	Percentage of Patients With Normalised Testosterone After 24 Weeks of Study Treatment
Description	Percentage of patients with normalised testosterone i.e. testosterone in the range 300-1000ng/dL after 24 weeks of study treatment. The primary objective was considered met, if greater than or equal to 75% of the participants in any arm normalised.
Time Frame	24 weeks of treatment

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	65	67	71
Count of Participants [Participants]	59 88.1%	62 93.9%	63 94%	7 9.9%

2. Secondary Outcome

Title	The Proportion of Subjects That Have Normalization of Total Testosterone Serum Concentrations From Baseline to Week 24
Description	Normalised total testosterone level was defined as between 300-1000 ng/dL (10.4-35 nmol/L) inclusive. Levels >1000 ng/dL were considered super-physiological outside the normal range.
Time Frame	Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	65	67	71
Baseline	7 10.4%	12 18.2%	11 16.4%	7 9.9%
Visit 2 (Day 8)	54 80.6%	53 80.3%	57 85.1%	7 9.9%
Visit 3 (Week 4)	63 94%	62 93.9%	64 95.5%	10 14.1%
Visit 4 (Week 8)	63 94%	61 92.4%	65 97%	11 15.5%
Visit 5 (Week 12)	58 86.6%	62 93.9%	64 95.5%	7 9.9%
Visit 6 (Week 16)	57 85.1%	63 95.5%	63 94%	8 11.3%
Visit 7 (Week 20)	57 85.1%	63 95.5%	66 98.5%	9 12.7%
Visit 8 (Week 24)	59 88.1%	62 93.9%	63 94%	7 9.9%

3. Secondary Outcome

Title	Proportion of Subjects That Overshoot Testosterone (Total Testosterone Above 1000 ng/dL [35 Nmol/L]) From Baseline to Week 24
Description	Testosterone overshoot was defined as total testosterone above 1000 ng/dL (35 nmol/L). Samples were collected in the morning before 11 am pre dose.
Time Frame	Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks

Outcome Measure Data

Analysis Population Description

ITT population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	65	67	71
Baseline	0 0%	0 0%	0 0%	0 0%
Visit 2 (Day 8)	0 0%	0 0%	0 0%	0 0%
Visit 3 (Week 4)	0 0%	0 0%	0 0%	0 0%
Visit 4 (Week 8)	0 0%	0 0%	1 1.5%	0 0%
Visit 5 (Week 12)	0 0%	0 0%	2 3%	2 2.8%
Visit 6 (Week 16)	0 0%	0 0%	2 3%	1 1.4%
Visit 7 (Week 20)	0 0%	0 0%	0 0%	1 1.4%
Visit 8 (Week 24)	0 0%	0 0%	1 1.5%	0 0%

4. Secondary Outcome

Title	Normalization of Total Testosterone Serum Concentrations in ≥ 90% Subjects After 24 Weeks of Treatment.
Description	Normalized total testosterone level was defined as between 300-1000 ng/dL (10.4-35 nmol/L) inclusive. Levels >1000 ng/dL were considered super-physiological outside the normal range. This secondary outcome measure was considered to have been met for a dose if ≥ 90% of subjects in the intent-to-treat (ITT) population had normalisation of total testosterone levels at Week 24.
Time Frame	24 weeks of treatment

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	65	67	71
Count of Participants [Participants]	59 88.1%	62 93.9%	63 94%	7 9.9%

5. Secondary Outcome

Title	Mean (SD) Change From Baseline in Luteinizing Hormone (LH) to Week 24.
Description	LH was measured at screening, baseline. The Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.
Time Frame	Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	65	67	71
Visit 2 (Day 8)	1.680 (1.7503)	2.095 (1.3719)	3.309 (1.8200)	-0.183 (1.3531)
Visit 3 (Week 4)	2.237 (2.1982)	3.626 (2.6519)	5.235 (4.8684)	-0.385 (1.2423)
Visit 4 (Week 8)	2.272 (2.1908)	3.653 (3.0907)	5.676 (4.1471)	-0.169 (1.5237)
Visit 5 (Week 12)	2.503 (2.2230)	3.511 (3.7050)	5.064 (3.9739)	-0.341 (1.4575)
Visit 6 (Week 16)	2.557 (1.6964)	3.704 (3.6269)	5.004 (4.3397)	-0.395 (1.4793)
Visit 7 (Week 20)	2.553 (2.2380)	3.653 (3.7381)	4.884 (3.9297)	-0.193 (1.3585)
Visit 8 (Week 24)	2.108 (1.9892)	3.560 (3.6138)	5.209 (4.4894)	-0.043 (1.5575)

6. Secondary Outcome

Title	Mean (SD) Change From Baseline in Follicle Stimulating Hormone (FSH) to Week 24.
Description	FSH was measured at baseline, Visit 1 through 8 and follow-up. Baseline was defined as the last non-missing value collected before the first study treatment administration, including unscheduled assessments.
Time Frame	Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks

Outcome Measure Data

Analysis Population Description

ITT Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	65	66	69
Visit 2 (Day 8)	3.553 (2.2022)	4.575 (2.0756)	5.307 (2.8315)	-0.51 (0.8273)
Visit 3 (Week 4)	4.158 (2.1353)	5.540 (2.8344)	6.551 (4.2155)	-0.111 (1.0638)
Visit 4 (Week 8)	4.318 (2.4147)	5.878 (2.9916)	7.620 (4.7883)	0.047 (1.2241)
Visit 5 (Week 12)	4.809 (2.5582)	5.768 (3.2474)	8.132 (5.9526)	-0.075 (1.0723)
Visit 6 (Week 16)	5.188 (2.6876)	6.350 (3.4261)	8.045 (6.1773)	-0.165 (1.1924)
Visit 7 (Week 20)	5.059 (2.5714)	6.073 (3.5199)	8.409 (6.6502)	-0.030 (1.0932)
Visit 8 (Week 24)	4.836 (2.6901)	6.183 (3.4817)	8.282 (7.0523)	0.038 (1.2164)

7. Secondary Outcome

Title	Descriptive Summary (Geometric Mean [95% CI]) of BGS649 Plasma PK Concentration Values to 24 Weeks.
Description	Plasma PK sampling for BGS649 was performed at Weeks 12 and 24. BGS649 PK plasma concentrations were summarised for the PK population by descriptive statistics.
Time Frame	Week 12 (pre-dose and 1 hour post-dose), week 24 and week 24/End of treatment

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	64	59	65
Visit 5 (Week 12), Pre-Dose	0.73	2.55	8.93
Visit 5 (Week 12), 1 hour Post-Dose	1.43	4.39	14.91
Visit 8 (Week 24)	0.85	2.97	10.04
Visit 8 (Week 24)/End of Treatment	0.78	2.76	9.10

8. Secondary Outcome

Title	Descriptive Summary (Geometric Mean [95% CI]) of BGS649 Semen PK Concentration Values at 24 Weeks.
Description	Semen PK sampling for BGS649 was performed at Visit 8 (End of Treatment). BGS649 PK semen concentrations were summarised for the PK population by descriptive statistics.
Time Frame	Week 24 and week 24/End of treatment

Outcome Measure Data

Analysis Population Description

PK population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	64	59	65
Visit 8 (Week 24)	0.51	1.95	5.81
Visit 8 (Week 24)/End of Treatment	0.49	1.58	5.28

9. Other Pre-specified Outcome

Title	Mean (SD) Change From Baseline in Prostate Specific Antigen (PSA) to Week 24.
Description	PSA was measured alongside other clinical chemistry parameters at screening, baseline, Visits 1 through 8 and at follow-up.
Time Frame	Baseline, Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	66	67	71
Visit 2 (Day 8)	0.045 (0.1840)	0.040 (0.4830)	0.011 (0.4606)	0.015 (0.2179)
Visit 3 (Week 4)	0.141 (0.1742)	0.082 (0.5198)	0.092 (0.4338)	0.038 (0.2700)
Visit 4 (Week 8)	0.166 (0.2651)	0.105 (0.4747)	0.132 (0.3343)	0.055 (0.4500)
Visit 5 (Week 12)	0.190 (0.3895)	0.271 (0.9626)	0.178 (0.5405)	0.039 (0.4382)
Visit 6 (Week 16)	0.147 (0.2655)	0.102 (0.5500)	0.160 (0.4037)	0.016 (0.2631)
Visit 7 (Week 20)	0.158 (0.2913)	0.480 (2.6029)	0.116 (0.4560)	0.022 (0.3942)
Visit 8 (Week 24)	0.218 (0.4312)	0.391 (1.8627)	0.085 (0.2930)	0.067 (0.4787)

10. Other Pre-specified Outcome

Title	Mean (SD) Change From Baseline in Haematocrit to Week 24.
Description	Haematocrit was measured alongside other haematology parameters at screening, baseline, Visits 1 through 8 and at follow-up.
Time Frame	Day 8, 4 weeks, 8 weeks, 12 weeks, 16 weeks, 20 weeks and 24 weeks

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	66	67	71
Visit 2 (Day 8)	-0.0003 (0.02279)	0.0014 (0.01945)	-0.0016 (0.03487)	-0.0029 (0.02374)
Visit 3 (Week 4)	0.0036 (0.01855)	0.0024 (0.02095)	0.0067 (0.02997)	-0.0024 (0.02539)
Visit 4 (Week 8)	0.0151 (0.02153)	0.0162 (0.02709)	0.0258 (0.03233)	-0.0041 (0.02383)
Visit 5 (Week 12)	0.0153 (0.02419)	0.0175 (0.02270)	0.0256 (0.02906)	-0.0082 (0.02882)
Visit 6 (Week 16)	0.0142 (0.02195)	0.0233 (0.02408)	0.0229 (0.03260)	-0.0079 (0.02533)
Visit 7 (Week 20)	0.0195 (0.02545)	0.0192 (0.02672)	0.0187 (0.03222)	-0.0063 (0.03037)
Visit 8 (Week 24)	0.0171 (0.02612)	0.0159 (0.02621)	0.0216 (0.02587)	-0.0032 (0.02884)

11. Other Pre-specified Outcome

Title	Mean (SD) Change From Baseline in Dual Energy X-ray Absorptiometry (DEXA) Scan T-score by Location at Week 24.
Description	Summary of DEXA Scan T-score at Visit 8 (Week 24) in the hip, femoral neck, and lumber spine. DEXA T-score was calculated based on actual measured bone density value and compared to a standard reference range for healthy young adult men.
Time Frame	Screening to Week 24

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	66	67	71
Hip	0.01 (0.382)	0.05 (0.315)	-0.02 (0.323)	0.01 (0.266)
Femoral neck	-0.16 (0.337)	0.02 (0.441)	-0.11 (0.392)	0.03 (0.212)
Lumber spine	-0.12 (0.279)	-0.08 (0.381)	-0.22 (0.351)	0.07 (0.346)

12. Other Pre-specified Outcome

Title	Mean (SD) Change From Baseline in DEXA Scan Density by Location at Week 24
Description	Summary of DEXA scan density at Visit 8 (Week 24) in the hip, femoral neck, and lumber spine. Bone density was evaluated with standard procedure for Hologic and General Electric Lunar scanners.
Time Frame	Screening to Week 24

Outcome Measure Data

Analysis Population Description

Safety Population

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	66	67	71
Hip	-0.0026 (0.03990)	-0.0020 (0.03828)	-0.0072 (0.02724)	0.0005 (0.03315)
Femoral neck	-0.0248 (0.04583)	-0.0044 (0.06666)	-0.0116 (0.05139)	0.0028 (0.02747)
Lumber spine	-0.0167 (0.03174)	-0.0177 (0.05018)	-0.0255 (0.04044)	0.0100 (0.04016)

13. Other Pre-specified Outcome

Title	Mean (SD) Change From Baseline in Bone Turnover Markers by Parameter at Week 24.
Description	Descriptive statistics were presented for the following bone turnover marker parameters: type I collagen C-telopeptides, procollagen 1 N-terminal propeptide, osteocalcin, and bone specific alkaline phosphatase.
Time Frame	Screening to Week 24

Outcome Measure Data

Analysis Population Description

ITT Population. Discrepancies in numbers from the progress flow are due to missing samples either at baseline or wk 24/EOT.

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	67	65	67	71
Type I Collagen C-Telopeptides	0.054 (0.1454)	0.069 (0.1618)	0.047 (0.1342)	0.020 (0.2087)
Procollagen 1 N-Terminal Propeptide	5.2 (8.31)	5.0 (11.93)	4.3 (11.68)	1.8 (11.61)
Osteocalcin	0.72 (2.891)	0.35 (3.801)	0.36 (3.604)	0.30 (3.267)

14. Other Pre-specified Outcome

Title	Change From Baseline in Bone Specific Alkaline Phosphatase at Week 24.
Description	Change from baseline in bone specific alkaline phosphatase at week 24 measured in U/L
Time Frame	24 weeks

Outcome Measure Data

Analysis Population Description

ITT population on all available samples and including all wk 24 and end-of-treatment visit data.

Arm/Group Title	BGS649 0.1 mg	BGS649 0.3 mg	BGS649 1.0 mg	Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks	Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
Measure Participants	58	51	56	55
Mean (Standard Deviation) [U/L]	0.15 (3.187)	0.69 (4.556)	0.03 (3.629)	0.29 (3.197)

Adverse Events

Time Frame	After randomisation and up to 90 days after the last administration of study drug.
Adverse Event Reporting Description	The following variables were recorded for each AE: verbatim/AE description and date for AE start and stop, severity, seriousness, causality rating, whether or not the AE caused the subject to discontinue, and the outcome. If the severity of the AE changed, a new AE had to be recorded. All ongoing AEs/SAEs were followed up until resolution or stabilisation or the last visit if in the Investigator's opinion, the AE was unlikely to resolve due to the subject's underlying disease.
Arm/Group Title	BGS649 0.1 mg		BGS649 0.3 mg		BGS649 1.0 mg		Placebo
Arm/Group Description	BGS649 0.1 mg weekly (1 BGS649 0.1 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks		BGS649 0.3 mg weekly (3 BGS649 0.1 mg capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks		BGS649 1.0 mg weekly (1 BGS649 1.0 mg capsule and 2 indistinguishable placebo capsules) BGS649: Capsules will be taken weekly for a maximum of 24 weeks		Placebo weekly (3 indistinguishable placebo capsules) Placebo: Capsules will be taken weekly for a maximum of 24 weeks
All Cause Mortality
	BGS649 0.1 mg		BGS649 0.3 mg		BGS649 1.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/67 (0%)		0/66 (0%)		0/67 (0%)		0/71 (0%)
Serious Adverse Events
	BGS649 0.1 mg		BGS649 0.3 mg		BGS649 1.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/67 (3%)		2/66 (3%)		5/67 (7.5%)		5/71 (7%)
Blood and lymphatic system disorders
Anaemia	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Cardiac disorders
Cardiac arrest	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Pericardial effusion	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Gastrointestinal disorders
Intestinal perforation	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
General disorders
Chest pain	1/67 (1.5%)	1	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Multiple organ dysfunction syndrome	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Infections and infestations
Postoperative wound infection	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	1/71 (1.4%)	1
Arthritis infective	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Diverticulitis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Osteomyelitis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	4	0/71 (0%)	0
Pneumonia	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Pyelonephritis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Sepsis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Injury, poisoning and procedural complications
Skull fracture	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Musculoskeletal and connective tissue disorders
Back pain	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Gouty arthritis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Nervous system disorders
Syncope	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Renal and urinary disorders
Acute kidney injury	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Ureterolithiasis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Respiratory, thoracic and mediastinal disorders
Respiratory failure	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Skin and subcutaneous tissue disorders
Diabetic foot	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Vascular disorders
Hypertension	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Other (Not Including Serious) Adverse Events
	BGS649 0.1 mg		BGS649 0.3 mg		BGS649 1.0 mg		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	37/67 (55.2%)		39/66 (59.1%)		47/67 (70.1%)		41/71 (57.7%)
Blood and lymphatic system disorders
Polycythaemia	3/67 (4.5%)	3	2/66 (3%)	2	0/67 (0%)	0	1/71 (1.4%)	1
Cardiac disorders
Atrial fibrillation	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Cyanosis	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Extrasystoles	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Left ventricular hypertrophy	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Ear and labyrinth disorders
Tinnitus	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Eye disorders
Dry eye	0/67 (0%)	0	0/66 (0%)	0	2/67 (3%)	2	0/71 (0%)	0
Blepharitis	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Gastrointestinal disorders
Diarrhoea	1/67 (1.5%)	1	2/66 (3%)	2	1/67 (1.5%)	1	2/71 (2.8%)	2
Constipation	1/67 (1.5%)	1	0/66 (0%)	0	1/67 (1.5%)	1	1/71 (1.4%)	2
Nausea	1/67 (1.5%)	1	0/66 (0%)	0	1/67 (1.5%)	1	1/71 (1.4%)	1
Vomiting	0/67 (0%)	0	1/66 (1.5%)	1	1/67 (1.5%)	1	1/71 (1.4%)	1
Abdominal discomfort	1/67 (1.5%)	1	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Dry mouth	0/67 (0%)	0	1/66 (1.5%)	1	1/67 (1.5%)	1	0/71 (0%)	0
Toothache	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	2	1/71 (1.4%)	1
Abdominal distension	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Dyspepsia	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Food poisoning	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Gastrooesophageal reflux disease	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Haematochezia	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
General disorders
Fatigue	1/67 (1.5%)	1	4/66 (6.1%)	4	1/67 (1.5%)	1	2/71 (2.8%)	2
Chest pain	0/67 (0%)	0	1/66 (1.5%)	1	1/67 (1.5%)	1	1/71 (1.4%)	1
Oedema peripheral	1/67 (1.5%)	1	0/66 (0%)	0	1/67 (1.5%)	1	1/71 (1.4%)	1
Influenza like illness	1/67 (1.5%)	1	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Asthenia	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Chest discomfort	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Cyst	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Energy increased	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Feeling hot	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Non-cardiac chest pain	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Oedema	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Pain	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Pyrexia	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Infections and infestations
Upper respiratory tract infection	3/67 (4.5%)	4	3/66 (4.5%)	4	2/67 (3%)	2	5/71 (7%)	5
Nasopharyngitis	2/67 (3%)	2	2/66 (3%)	2	1/67 (1.5%)	1	1/71 (1.4%)	1
Sinusitis	1/67 (1.5%)	1	1/66 (1.5%)	1	0/67 (0%)	0	2/71 (2.8%)	2
Influenza	0/67 (0%)	0	1/66 (1.5%)	1	1/67 (1.5%)	1	1/71 (1.4%)	1
Urinary tract infection	0/67 (0%)	0	2/66 (3%)	2	0/67 (0%)	0	1/71 (1.4%)	2
Gastroenteritis	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	1/71 (1.4%)	1
Osteomyelitis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Pneumonia	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Sepsis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Tooth abscess	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Tooth infection	1/67 (1.5%)	1	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Bacterial prostatitis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Bronchitis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Conjunctivitis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Ear infection	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Folliculitis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Furuncle	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Gastritis viral	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Gastroenteritis norovirus	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Lower respiratory tract infection	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Oral herpes	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Otitis externa	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Otitis media	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Otitis media acute	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Rash pustular	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	2	0/71 (0%)	0
Respiratory tract infection	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Tinea pedis	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Viral upper respiratory tract infection	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Injury, poisoning and procedural complications
Back injury	0/67 (0%)	0	1/66 (1.5%)	2	1/67 (1.5%)	1	0/71 (0%)	0
Contusion	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	1/71 (1.4%)	1
Fall	0/67 (0%)	0	0/66 (0%)	0	2/67 (3%)	2	0/71 (0%)	0
Limb injury	0/67 (0%)	0	0/66 (0%)	0	2/67 (3%)	2	0/71 (0%)	0
Muscle strain	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Animal bite	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Arthropod sting	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Excoriation	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Laceration	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Procedural pain	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Radius fracture	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Skin abrasion	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Tendon rupture	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Thermal burn	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Tooth fracture	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Investigations
Haematocrit increased	1/67 (1.5%)	2	4/66 (6.1%)	5	5/67 (7.5%)	6	0/71 (0%)	0
Prostatic specific antigen increased	2/67 (3%)	2	1/66 (1.5%)	1	4/67 (6%)	4	2/71 (2.8%)	2
Blood triglycerides increased	0/67 (0%)	0	2/66 (3%)	2	1/67 (1.5%)	1	2/71 (2.8%)	2
Weight increased	0/67 (0%)	0	1/66 (1.5%)	1	2/67 (3%)	2	1/71 (1.4%)	1
Blood creatinine increased	1/67 (1.5%)	1	0/66 (0%)	0	1/67 (1.5%)	1	1/71 (1.4%)	1
Blood pressure increased	0/67 (0%)	0	1/66 (1.5%)	1	2/67 (3%)	2	0/71 (0%)	0
Aspartate aminotransferase increased	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	1/71 (1.4%)	2
Hepatic enzyme increased	1/67 (1.5%)	1	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Alanine aminotransferase increased	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Blood bilirubin increased	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Blood glucose increased	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Blood insulin increased	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Blood pressure decreased	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Blood prolactin increased	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Blood urine present	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
C-reactive protein increased	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Electrocardiogram QT prolonged	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Glycosylated haemoglobin increased	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Heart rate irregular	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Low density lipoprotein increased	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Metabolism and nutrition disorders
Vitamin D deficiency	2/67 (3%)	2	2/66 (3%)	2	1/67 (1.5%)	1	0/71 (0%)	0
Diabetes mellitus	1/67 (1.5%)	1	1/66 (1.5%)	1	1/67 (1.5%)	1	0/71 (0%)	0
Hypertriglyceridaemia	1/67 (1.5%)	1	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Type 2 diabetes mellitus	1/67 (1.5%)	1	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Fluid retention	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Gout	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Hypochloraemia	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Hypoglycaemia	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Hypokalaemia	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Hyponatraemia	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Increased appetite	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Musculoskeletal and connective tissue disorders
Arthralgia	3/67 (4.5%)	3	3/66 (4.5%)	3	1/67 (1.5%)	1	1/71 (1.4%)	1
Back pain	2/67 (3%)	2	2/66 (3%)	2	2/67 (3%)	2	1/71 (1.4%)	1
Muscle spasms	2/67 (3%)	2	2/66 (3%)	2	0/67 (0%)	0	1/71 (1.4%)	1
Myalgia	1/67 (1.5%)	1	1/66 (1.5%)	1	0/67 (0%)	0	2/71 (2.8%)	2
Pain in extremity	1/67 (1.5%)	1	0/66 (0%)	0	3/67 (4.5%)	3	0/71 (0%)	0
Osteopenia	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	2/71 (2.8%)	2
Bursitis	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Groin pain	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Intervertebral disc protrusion	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Osteoarthritis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	3	0/71 (0%)	0
Psoriatic arthropathy	1/67 (1.5%)	2	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Rotator cuff syndrome	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Spinal column stenosis	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Trigger finger	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal cell carcinoma	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Seborrhoeic keratosis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Squamous cell carcinoma	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Nervous system disorders
Headache	7/67 (10.4%)	8	3/66 (4.5%)	4	4/67 (6%)	4	2/71 (2.8%)	3
Dizziness	3/67 (4.5%)	3	0/66 (0%)	0	2/67 (3%)	2	0/71 (0%)	0
Paraesthesia	0/67 (0%)	0	1/66 (1.5%)	1	1/67 (1.5%)	1	0/71 (0%)	0
Syncope	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Central nervous system lesion	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Complex regional pain syndrome	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Facial paralysis	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Lethargy	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Metabolic encephalopathy	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Migraine	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Neuralgia	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Presyncope	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Primary headache associated with sexual activity	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Sensory loss	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Tremor	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Psychiatric disorders
Insomnia	2/67 (3%)	2	0/66 (0%)	0	2/67 (3%)	2	0/71 (0%)	0
Depression	0/67 (0%)	0	3/66 (4.5%)	3	0/67 (0%)	0	0/71 (0%)	0
Libido decreased	1/67 (1.5%)	1	1/66 (1.5%)	1	1/67 (1.5%)	1	0/71 (0%)	0
Irritability	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	1/71 (1.4%)	2
Adjustment disorder with depressed mood	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Agitation	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Anxiety	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Apathy	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Euphoric mood	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Loss of libido	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Mood altered	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Renal and urinary disorders
Pollakiuria	1/67 (1.5%)	1	1/66 (1.5%)	1	1/67 (1.5%)	1	0/71 (0%)	0
Nephrolithiasis	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Bladder outlet obstruction	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Calculus urinary	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Chronic kidney disease	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Glycosuria	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Haematuria	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Hydronephrosis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Micturition urgency	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Nocturia	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Renal cyst	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Urinary retention	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Urinary tract obstruction	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Reproductive system and breast disorders
Erectile dysfunction	0/67 (0%)	0	1/66 (1.5%)	1	1/67 (1.5%)	1	0/71 (0%)	0
Gynaecomastia	2/67 (3%)	2	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Testicular pain	1/67 (1.5%)	1	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Breast pain	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Erection increased	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Prostatic mass	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Prostatomegaly	0/67 (0%)	0	1/66 (1.5%)	1	0/67 (0%)	0	0/71 (0%)	0
Spontaneous penile erection	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Testicular hypertrophy	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Respiratory, thoracic and mediastinal disorders
Cough	1/67 (1.5%)	1	0/66 (0%)	0	3/67 (4.5%)	3	1/71 (1.4%)	1
Nasal congestion	2/67 (3%)	2	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Oropharyngeal pain	0/67 (0%)	0	1/66 (1.5%)	1	1/67 (1.5%)	1	0/71 (0%)	0
Asthma	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Bronchial hyperreactivity	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Dyspnoea	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Epistaxis	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Pickwickian syndrome	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Productive cough	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Respiratory failure	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Rhinitis allergic	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Sinus congestion	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Sleep apnoea syndrome	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	2	0/71 (0%)	0
Skin and subcutaneous tissue disorders
Rash	1/67 (1.5%)	1	1/66 (1.5%)	1	2/67 (3%)	2	1/71 (1.4%)	1
Dermatitis contact	1/67 (1.5%)	2	1/66 (1.5%)	1	0/67 (0%)	0	1/71 (1.4%)	1
Pruritus	0/67 (0%)	0	0/66 (0%)	0	2/67 (3%)	2	0/71 (0%)	0
Alopecia	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Androgenetic alopecia	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Blister	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Dermatitis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Diabetic foot	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Hidradenitis	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Night sweats	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Onycholysis	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Penile ulceration	1/67 (1.5%)	1	0/66 (0%)	0	0/67 (0%)	0	0/71 (0%)	0
Seborrhoea	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0
Vascular disorders
Hypertension	2/67 (3%)	2	2/66 (3%)	2	5/67 (7.5%)	5	0/71 (0%)	0
Haematoma	0/67 (0%)	0	0/66 (0%)	0	0/67 (0%)	0	1/71 (1.4%)	1
Hot flush	0/67 (0%)	0	0/66 (0%)	0	1/67 (1.5%)	1	0/71 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.