Hypogonadotropic Hypogonadism
Conditions
Keywords
Hypogonadotropic, hypogonadism, testosterone
Brief summary
Phase IIb, multicentre, double-blind, randomised, placebo-controlled parallel-group 36-week study evaluating safety and efficacy of BGS649 in male obese subjects with hypogonadotropic hypogonadism (HH)
Detailed description
This is a 6 months, active treatment, extension study, open to subjects who have completed full 24 weeks in Study MBGS205 (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 \[HH\]).The main purpose of Study MBGS206 is to evaluate long term safety and efficacy parameters in subjects after 12 months exposure with BGS649.
Interventions
DRUGBGS649
Capsules will be taken weekly for a maximum of 24 weeks
Sponsors
Mereo BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
MALE
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Participating in Study MBGS205 and completion of the 24 week treatment period without meeting any discontinuation criteria of Study MBGS205 * In opinion of the investigator has been compliant with the requirements of the Study MBGS205 protocol.
Exclusion criteria
-Meeting any of the discontinuation criteria of initial Study MBGS205
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Change in Bone Mineral Density Measured by DEXA (g/cm^2) From Baseline in Study MBGS205 to Week 48 in Study MBGS206 | At 48 weeks compared to baseline in MBGS205 | Percentage change in lumbar bone mineral density measured by DEXA (g/cm\^2) from Baseline in Study MBGS205 to Week 48 in Study MBGS206 by dose group in participants randomised to active treatment in MBGS205. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | 48 Weeks | Percentage change from baseline in bone turnover markers (C-terminal telopeptide \[CTx1\], osteocalcin, bone alkaline phosphatase, and procollagen type 1 N-propeptide \[P1NP\]) from Baseline in Study MBGS205 to Week 48 in Study MBGS206 |
| Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | 48 Weeks | Proportion of subjects with DEXA scan T- scores ≤ -2.5 at Week 48 in MBGS206 compared to baseline in MBGS205 by body location (using overread scan images). |
| Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | 48 Weeks | Percentage change from baseline in bone density and bone biomarkers for vitamin D deficiency from Baseline in Study MBGS205 to Week 48 in Study MBGS206. Bone mineral density (g/cm\^2) measured by DEXA over-read by a central reader. |
| Change From Baseline of Oestradiol (Absolute) From Baseline in Study MBGS205 to Week 48 | 48 Weeks | Descriptive Summary of Oestradiol and Testosterone/Oestradiol Ratio for Subjects Randomised to Active Treatment in Study MBGS205 |
| Change From Baseline of Oestradiol (Percentage) From Baseline in Study MBGS205 to Week 48 | 48 Weeks | Descriptive Summary of Percentage Change in Oestradiol and Testosterone/Oestradiol Ratio for Subjects Randomised to Active Treatment in Study MBGS205 |
| Analysis of Proportion of Subjects That Overshoot Testosterone for Subjects Randomised to Active Treatment in Study MBGS205 | 48 Weeks | Proportion of subjects that overshoot testosterone (total testosterone above 1000 ng/dl \[35 nmol/L\], from first dose of study drug in Study MBGS205 until study completion) |
| Change From Baseline in PSA From Baseline in Study MBGS205 to Week 48 in Study MBGS206 | 48 Weeks | Summary of Laboratory Test Results and Change from Baseline: PSA for Subjects Randomised to Active Treatment in Study MBGS205 |
| Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | 48 Weeks | Percentage change from baseline in hip (total and femoral neck) bone mineral density measured by DEXA (g/cm\^2) from Baseline in Study MBGS205 to Week 48 in Study MBGS206 |
| Change From Baseline in Blood Pressure From Baseline to Week 48MBGS205 | 48 Weeks | Change from baseline in blood pressure (systolic and diastolic measured in mmHg) Baseline in Study MBGS205 to Week 48 in Study MBGS206. |
| Percentage of Subjects Achieving Normalisation of Bioavailable (Total) Testosterone at Wk 48 | 48 Weeks | Percentage of subjects where bioavailable testosterone was normalised at week 48 in Study MBGS206. Where normalisation was considered testosterone in the range 300-1000 mg/dL. |
| Descriptive Summary of Total Testosterone (ng/dL) for Subjects Randomised to Active Treatment in Study MBGS205 | 48 Weeks | Change from baseline in total, free and bioavailable testosterone from Baseline in Study MBGS205 to Week 48 in Study MBGS206 |
| Change From Baseline in Free and Bioavailable Testosterone | 48 Weeks | Change from baseline in free and bioavailable (total) testosterone from baseline in Study MBGS205 to Week 48 in Study MBGS206. |
| Change From Baseline in Luteinizing Hormone From Baseline to Week 48 | 48 Weeks | Change from baseline of LH from Baseline in Study MBGS205 to Week 48 in Study MBGS206. |
| Change From Baseline in Follicle Stimulating Hormone at Week 48 | 48 Weeks | Change from Baseline in Study MBGS205 to Week 48 in Study MBGS206 in follicle stimulating hormone (FSH). |
| Percentage Change in Bone Alkaline Phosphatase | 48 weeks | Percentage change in baseline in alkaline phosphatase from baseline in study MBGS205 to week 48 in MBGS206. |
| Change From Baseline in Haematocrit at Week 48 | 48 Weeks | Change from baseline in haematocrit from Baseline in Study MBGS205 to Week 48 in Study MBGS206 |
Countries
United States
Participant flow
Pre-assignment details
Participants receiving active doses of BGS649 in Study MBGS205 continued with the same dose in Study MBGS206; Participants receiving placebo in Study MBGS205 were re-randomised at the Baseline visit to receive one of the 3 treatment regimens (BGS649 0.1 mg, 0.3 mg, and 1.0 mg) in a 1:1:1 ratio, and were only assessed for safety in study MBGS206.
Participants by arm
| Arm | Count |
|---|---|
| BGS649 0.1 mg Drug: BGS649 Dose 1 weekly
BGS649: Capsules will be taken weekly for a maximum of 24 weeks | 38 |
| BGS649 0.3 mg Drug: BGS649 Dose 2 weekly
BGS649: Capsules will be taken weekly for a maximum of 24 weeks | 33 |
| BGS649 1.0 mg Drug: BGS649 Dose 3 weekly
BGS649: Capsules will be taken weekly for a maximum of 24 weeks | 30 |
| Placebo to BGS649 0.1 mg Drug: BGS649 Dose 1 weekly
BGS649: Capsules will be taken weekly for a maximum of 24 weeks | 13 |
| Placebo to BGS649 0.3 mg Drug: BGS649 Dose 2 weekly
BGS649: Capsules will be taken weekly for a maximum of 24 weeks | 17 |
| Placebo to BGS649 1.0 mg Drug: BGS649 Dose 3 weekly
BGS649: Capsules will be taken weekly for a maximum of 24 weeks | 10 |
| Total | 141 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 |
|---|---|---|---|---|---|---|---|
| Overall Study | Adverse Event | 5 | 2 | 0 | 0 | 1 | 0 |
| Overall Study | AESI | 1 | 0 | 1 | 0 | 1 | 0 |
| Overall Study | Discontinuation criteria per protocol | 0 | 0 | 1 | 0 | 0 | 1 |
| Overall Study | Lost to Follow-up | 0 | 1 | 1 | 1 | 0 | 1 |
| Overall Study | Protocol Violation | 0 | 1 | 0 | 0 | 0 | 0 |
| Overall Study | sponsor/ICON decision | 0 | 0 | 1 | 0 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 2 | 2 | 2 | 2 | 2 |
Baseline characteristics
| Characteristic | BGS649 0.1 mg | Total | Placebo to BGS649 1.0 mg | Placebo to BGS649 0.3 mg | Placebo to BGS649 0.1 mg | BGS649 1.0 mg | BGS649 0.3 mg |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 52.2 years STANDARD_DEVIATION 7.34 | 51.0 years STANDARD_DEVIATION 8.6 | 51.1 years STANDARD_DEVIATION 8.32 | 49.8 years STANDARD_DEVIATION 8.93 | 48.9 years STANDARD_DEVIATION 11.04 | 50.0 years STANDARD_DEVIATION 9.98 | 51.9 years STANDARD_DEVIATION 7.76 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 8 Participants | 29 Participants | 2 Participants | 1 Participants | 1 Participants | 9 Participants | 8 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 3 Participants | 0 Participants | 0 Participants | 1 Participants | 0 Participants | 2 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 30 Participants | 106 Participants | 8 Participants | 15 Participants | 11 Participants | 19 Participants | 23 Participants |
| Sex: Female, Male Female | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Sex: Female, Male Male | 38 Participants | 141 Participants | 10 Participants | 17 Participants | 13 Participants | 30 Participants | 33 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 38 | 1 / 33 | 0 / 30 | 0 / 13 | 0 / 17 | 0 / 10 |
| other Total, other adverse events | 27 / 38 | 23 / 33 | 25 / 30 | 10 / 13 | 12 / 17 | 6 / 10 |
| serious Total, serious adverse events | 1 / 38 | 2 / 33 | 1 / 30 | 0 / 13 | 0 / 17 | 0 / 10 |
Outcome results
Primary
Percent Change in Bone Mineral Density Measured by DEXA (g/cm^2) From Baseline in Study MBGS205 to Week 48 in Study MBGS206
Percentage change in lumbar bone mineral density measured by DEXA (g/cm\^2) from Baseline in Study MBGS205 to Week 48 in Study MBGS206 by dose group in participants randomised to active treatment in MBGS205.
Time frame: At 48 weeks compared to baseline in MBGS205
Population: The Intention-to-treat (ITT) population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine bone mineral density (BMD) measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Percent Change in Bone Mineral Density Measured by DEXA (g/cm^2) From Baseline in Study MBGS205 to Week 48 in Study MBGS206 | -2.24 Percentage change | Standard Deviation 3.157 |
| BGS649 0.3 mg | Percent Change in Bone Mineral Density Measured by DEXA (g/cm^2) From Baseline in Study MBGS205 to Week 48 in Study MBGS206 | -3.31 Percentage change | Standard Deviation 5.301 |
| BGS649 1.0 mg | Percent Change in Bone Mineral Density Measured by DEXA (g/cm^2) From Baseline in Study MBGS205 to Week 48 in Study MBGS206 | -1.68 Percentage change | Standard Deviation 3.095 |
Secondary
Analysis of Proportion of Subjects That Overshoot Testosterone for Subjects Randomised to Active Treatment in Study MBGS205
Proportion of subjects that overshoot testosterone (total testosterone above 1000 ng/dl \[35 nmol/L\], from first dose of study drug in Study MBGS205 until study completion)
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGS649 0.1 mg | Analysis of Proportion of Subjects That Overshoot Testosterone for Subjects Randomised to Active Treatment in Study MBGS205 | 0 Participants |
| BGS649 0.3 mg | Analysis of Proportion of Subjects That Overshoot Testosterone for Subjects Randomised to Active Treatment in Study MBGS205 | 0 Participants |
| BGS649 1.0 mg | Analysis of Proportion of Subjects That Overshoot Testosterone for Subjects Randomised to Active Treatment in Study MBGS205 | 2 Participants |
Secondary
Change From Baseline in Blood Pressure From Baseline to Week 48MBGS205
Change from baseline in blood pressure (systolic and diastolic measured in mmHg) Baseline in Study MBGS205 to Week 48 in Study MBGS206.
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BGS649 0.1 mg | Change From Baseline in Blood Pressure From Baseline to Week 48MBGS205 | Systolic Blood Pressure | 2.7 Blood Pressure (mmHg) (Change) | Standard Deviation 7.13 |
| BGS649 0.1 mg | Change From Baseline in Blood Pressure From Baseline to Week 48MBGS205 | Diastolic Blood Pressure | -0.2 Blood Pressure (mmHg) (Change) | Standard Deviation 8.12 |
| BGS649 0.3 mg | Change From Baseline in Blood Pressure From Baseline to Week 48MBGS205 | Systolic Blood Pressure | 2.6 Blood Pressure (mmHg) (Change) | Standard Deviation 12.64 |
| BGS649 0.3 mg | Change From Baseline in Blood Pressure From Baseline to Week 48MBGS205 | Diastolic Blood Pressure | 1.1 Blood Pressure (mmHg) (Change) | Standard Deviation 4.41 |
| BGS649 1.0 mg | Change From Baseline in Blood Pressure From Baseline to Week 48MBGS205 | Systolic Blood Pressure | -0.7 Blood Pressure (mmHg) (Change) | Standard Deviation 8.34 |
| BGS649 1.0 mg | Change From Baseline in Blood Pressure From Baseline to Week 48MBGS205 | Diastolic Blood Pressure | 1.6 Blood Pressure (mmHg) (Change) | Standard Deviation 8.3 |
Secondary
Change From Baseline in Follicle Stimulating Hormone at Week 48
Change from Baseline in Study MBGS205 to Week 48 in Study MBGS206 in follicle stimulating hormone (FSH).
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Change From Baseline in Follicle Stimulating Hormone at Week 48 | 5.473 Follicle Stimulating Hormone (mIU/mL) | Standard Deviation 2.9494 |
| BGS649 0.3 mg | Change From Baseline in Follicle Stimulating Hormone at Week 48 | 7.509 Follicle Stimulating Hormone (mIU/mL) | Standard Deviation 3.0235 |
| BGS649 1.0 mg | Change From Baseline in Follicle Stimulating Hormone at Week 48 | 6.781 Follicle Stimulating Hormone (mIU/mL) | Standard Deviation 5.2389 |
Secondary
Change From Baseline in Free and Bioavailable Testosterone
Change from baseline in free and bioavailable (total) testosterone from baseline in Study MBGS205 to Week 48 in Study MBGS206.
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BGS649 0.1 mg | Change From Baseline in Free and Bioavailable Testosterone | Bioavailable Testosterone (ng/dL) | 162.12 (ng/dL) and (ng/L), respectively | Standard Deviation 70.686 |
| BGS649 0.1 mg | Change From Baseline in Free and Bioavailable Testosterone | Testosterone, Free (ng/L) | 60.28 (ng/dL) and (ng/L), respectively | Standard Deviation 25.02 |
| BGS649 0.3 mg | Change From Baseline in Free and Bioavailable Testosterone | Bioavailable Testosterone (ng/dL) | 191.23 (ng/dL) and (ng/L), respectively | Standard Deviation 76.431 |
| BGS649 0.3 mg | Change From Baseline in Free and Bioavailable Testosterone | Testosterone, Free (ng/L) | 72.65 (ng/dL) and (ng/L), respectively | Standard Deviation 26.674 |
| BGS649 1.0 mg | Change From Baseline in Free and Bioavailable Testosterone | Bioavailable Testosterone (ng/dL) | 255.57 (ng/dL) and (ng/L), respectively | Standard Deviation 103.758 |
| BGS649 1.0 mg | Change From Baseline in Free and Bioavailable Testosterone | Testosterone, Free (ng/L) | 94.82 (ng/dL) and (ng/L), respectively | Standard Deviation 35.674 |
| Placebo to BGS649 0.1 mg | Change From Baseline in Free and Bioavailable Testosterone | Bioavailable Testosterone (ng/dL) | 168.71 (ng/dL) and (ng/L), respectively | Standard Deviation 111.634 |
| Placebo to BGS649 0.1 mg | Change From Baseline in Free and Bioavailable Testosterone | Testosterone, Free (ng/L) | 61.01 (ng/dL) and (ng/L), respectively | Standard Deviation 40.632 |
| Placebo to BGS649 0.3 mg | Change From Baseline in Free and Bioavailable Testosterone | Bioavailable Testosterone (ng/dL) | 240.25 (ng/dL) and (ng/L), respectively | Standard Deviation 111.842 |
| Placebo to BGS649 0.3 mg | Change From Baseline in Free and Bioavailable Testosterone | Testosterone, Free (ng/L) | 84.62 (ng/dL) and (ng/L), respectively | Standard Deviation 38.353 |
| Placebo to BGS649 1.0 mg | Change From Baseline in Free and Bioavailable Testosterone | Bioavailable Testosterone (ng/dL) | 255.27 (ng/dL) and (ng/L), respectively | Standard Deviation 111.674 |
| Placebo to BGS649 1.0 mg | Change From Baseline in Free and Bioavailable Testosterone | Testosterone, Free (ng/L) | 90.47 (ng/dL) and (ng/L), respectively | Standard Deviation 37.064 |
Secondary
Change From Baseline in Haematocrit at Week 48
Change from baseline in haematocrit from Baseline in Study MBGS205 to Week 48 in Study MBGS206
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Change From Baseline in Haematocrit at Week 48 | 0.0128 RATIO (Change) | Standard Deviation 0.02273 |
| BGS649 0.3 mg | Change From Baseline in Haematocrit at Week 48 | 0.0136 RATIO (Change) | Standard Deviation 0.02517 |
| BGS649 1.0 mg | Change From Baseline in Haematocrit at Week 48 | 0.0286 RATIO (Change) | Standard Deviation 0.0341 |
Secondary
Change From Baseline in Luteinizing Hormone From Baseline to Week 48
Change from baseline of LH from Baseline in Study MBGS205 to Week 48 in Study MBGS206.
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Change From Baseline in Luteinizing Hormone From Baseline to Week 48 | 2.683 Luteinizing Hormone (mIU/mL) | Standard Deviation 1.6586 |
| BGS649 0.3 mg | Change From Baseline in Luteinizing Hormone From Baseline to Week 48 | 3.665 Luteinizing Hormone (mIU/mL) | Standard Deviation 2.3477 |
| BGS649 1.0 mg | Change From Baseline in Luteinizing Hormone From Baseline to Week 48 | 3.613 Luteinizing Hormone (mIU/mL) | Standard Deviation 2.7807 |
| Placebo to BGS649 0.1 mg | Change From Baseline in Luteinizing Hormone From Baseline to Week 48 | 3.973 Luteinizing Hormone (mIU/mL) | Standard Deviation 4.142 |
| Placebo to BGS649 0.3 mg | Change From Baseline in Luteinizing Hormone From Baseline to Week 48 | 4.834 Luteinizing Hormone (mIU/mL) | Standard Deviation 3.193 |
| Placebo to BGS649 1.0 mg | Change From Baseline in Luteinizing Hormone From Baseline to Week 48 | 2.720 Luteinizing Hormone (mIU/mL) | Standard Deviation 0.5071 |
Secondary
Change From Baseline in PSA From Baseline in Study MBGS205 to Week 48 in Study MBGS206
Summary of Laboratory Test Results and Change from Baseline: PSA for Subjects Randomised to Active Treatment in Study MBGS205
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Change From Baseline in PSA From Baseline in Study MBGS205 to Week 48 in Study MBGS206 | 0.163 Prostate Specific Antigen (ug/L) | Standard Deviation 0.2454 |
| BGS649 0.3 mg | Change From Baseline in PSA From Baseline in Study MBGS205 to Week 48 in Study MBGS206 | 0.164 Prostate Specific Antigen (ug/L) | Standard Deviation 0.641 |
| BGS649 1.0 mg | Change From Baseline in PSA From Baseline in Study MBGS205 to Week 48 in Study MBGS206 | 0.169 Prostate Specific Antigen (ug/L) | Standard Deviation 0.6246 |
Secondary
Change From Baseline of Oestradiol (Absolute) From Baseline in Study MBGS205 to Week 48
Descriptive Summary of Oestradiol and Testosterone/Oestradiol Ratio for Subjects Randomised to Active Treatment in Study MBGS205
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Change From Baseline of Oestradiol (Absolute) From Baseline in Study MBGS205 to Week 48 | -12.750 Oestradiol (pg/mL) | Standard Deviation 13.4264 |
| BGS649 0.3 mg | Change From Baseline of Oestradiol (Absolute) From Baseline in Study MBGS205 to Week 48 | -11.852 Oestradiol (pg/mL) | Standard Deviation 5.682 |
| BGS649 1.0 mg | Change From Baseline of Oestradiol (Absolute) From Baseline in Study MBGS205 to Week 48 | -12.917 Oestradiol (pg/mL) | Standard Deviation 9.0117 |
Secondary
Change From Baseline of Oestradiol (Percentage) From Baseline in Study MBGS205 to Week 48
Descriptive Summary of Percentage Change in Oestradiol and Testosterone/Oestradiol Ratio for Subjects Randomised to Active Treatment in Study MBGS205
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Change From Baseline of Oestradiol (Percentage) From Baseline in Study MBGS205 to Week 48 | -39.54 percentage from baseline at Week 48 | Standard Deviation 33.295 |
| BGS649 0.3 mg | Change From Baseline of Oestradiol (Percentage) From Baseline in Study MBGS205 to Week 48 | -47.00 percentage from baseline at Week 48 | Standard Deviation 17.852 |
| BGS649 1.0 mg | Change From Baseline of Oestradiol (Percentage) From Baseline in Study MBGS205 to Week 48 | -48.30 percentage from baseline at Week 48 | Standard Deviation 19.752 |
Secondary
Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205
Percentage change from baseline in bone turnover markers (C-terminal telopeptide \[CTx1\], osteocalcin, bone alkaline phosphatase, and procollagen type 1 N-propeptide \[P1NP\]) from Baseline in Study MBGS205 to Week 48 in Study MBGS206
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BGS649 0.1 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | Procollagen 1 N-Terminal Propeptide | 40.40 ug/L | Standard Deviation 32.108 |
| BGS649 0.1 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | 2Type I Collagen C-Telopeptides | 83.28 ug/L | Standard Deviation 164.647 |
| BGS649 0.1 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | Osteocalcin | 13.79 ug/L | Standard Deviation 17.525 |
| BGS649 0.3 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | Procollagen 1 N-Terminal Propeptide | 37.62 ug/L | Standard Deviation 44.742 |
| BGS649 0.3 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | 2Type I Collagen C-Telopeptides | 64.42 ug/L | Standard Deviation 64.473 |
| BGS649 0.3 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | Osteocalcin | 18.86 ug/L | Standard Deviation 28.545 |
| BGS649 1.0 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | 2Type I Collagen C-Telopeptides | 57.91 ug/L | Standard Deviation 82.289 |
| BGS649 1.0 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | Osteocalcin | 15.28 ug/L | Standard Deviation 25.98 |
| BGS649 1.0 mg | Descriptive Summary of Percentage Change in Bone Turnover Markers for Subjects Randomised to Active Treatment in Study MBGS205 | Procollagen 1 N-Terminal Propeptide | 34.17 ug/L | Standard Deviation 35.017 |
Secondary
Descriptive Summary of Total Testosterone (ng/dL) for Subjects Randomised to Active Treatment in Study MBGS205
Change from baseline in total, free and bioavailable testosterone from Baseline in Study MBGS205 to Week 48 in Study MBGS206
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Descriptive Summary of Total Testosterone (ng/dL) for Subjects Randomised to Active Treatment in Study MBGS205 | 241.0 Total Testosterone (ng/dL) Change | Standard Deviation 99.14 |
| BGS649 0.3 mg | Descriptive Summary of Total Testosterone (ng/dL) for Subjects Randomised to Active Treatment in Study MBGS205 | 290.6 Total Testosterone (ng/dL) Change | Standard Deviation 109.64 |
| BGS649 1.0 mg | Descriptive Summary of Total Testosterone (ng/dL) for Subjects Randomised to Active Treatment in Study MBGS205 | 378.9 Total Testosterone (ng/dL) Change | Standard Deviation 158.67 |
Secondary
Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency
Percentage change from baseline in bone density and bone biomarkers for vitamin D deficiency from Baseline in Study MBGS205 to Week 48 in Study MBGS206. Bone mineral density (g/cm\^2) measured by DEXA over-read by a central reader.
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated for each location.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BGS649 0.1 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Femoral Neck) (g/cm2) | -1.93 percentage change from baseline in DEXA | Standard Deviation 5.743 |
| BGS649 0.1 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Hip) (g/cm2) | -0.86 percentage change from baseline in DEXA | Standard Deviation 3.129 |
| BGS649 0.1 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Lumbar Spine) (g/cm2) | -2.10 percentage change from baseline in DEXA | Standard Deviation 3.623 |
| BGS649 0.3 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Femoral Neck) (g/cm2) | -2.27 percentage change from baseline in DEXA | Standard Deviation 6.739 |
| BGS649 0.3 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Hip) (g/cm2) | -1.81 percentage change from baseline in DEXA | Standard Deviation 3.684 |
| BGS649 0.3 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Lumbar Spine) (g/cm2) | -3.86 percentage change from baseline in DEXA | Standard Deviation 5.966 |
| BGS649 1.0 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Femoral Neck) (g/cm2) | 0.19 percentage change from baseline in DEXA | Standard Deviation 5.161 |
| BGS649 1.0 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Hip) (g/cm2) | 1.22 percentage change from baseline in DEXA | Standard Deviation 4.532 |
| BGS649 1.0 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Lumbar Spine) (g/cm2) | -2.01 percentage change from baseline in DEXA | Standard Deviation 3.52 |
| Placebo to BGS649 0.1 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Femoral Neck) (g/cm2) | -0.56 percentage change from baseline in DEXA | Standard Deviation 4.485 |
| Placebo to BGS649 0.1 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Hip) (g/cm2) | -0.78 percentage change from baseline in DEXA | Standard Deviation 3.91 |
| Placebo to BGS649 0.1 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Lumbar Spine) (g/cm2) | 1.54 percentage change from baseline in DEXA | Standard Deviation 4.463 |
| Placebo to BGS649 0.3 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Femoral Neck) (g/cm2) | 0.16 percentage change from baseline in DEXA | Standard Deviation 2.64 |
| Placebo to BGS649 0.3 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Hip) (g/cm2) | 0.09 percentage change from baseline in DEXA | Standard Deviation 1.497 |
| Placebo to BGS649 0.3 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Lumbar Spine) (g/cm2) | -0.08 percentage change from baseline in DEXA | Standard Deviation 2.017 |
| Placebo to BGS649 1.0 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Hip) (g/cm2) | 4.36 percentage change from baseline in DEXA | — |
| Placebo to BGS649 1.0 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Lumbar Spine) (g/cm2) | -3.12 percentage change from baseline in DEXA | Standard Deviation 1.691 |
| Placebo to BGS649 1.0 mg | Percentage Change From Baseline in Bone Mineral Density by Location and Vitamin D Deficiency | Bone Density (Femoral Neck) (g/cm2) | 3.02 percentage change from baseline in DEXA | — |
Secondary
Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read)
Percentage change from baseline in hip (total and femoral neck) bone mineral density measured by DEXA (g/cm\^2) from Baseline in Study MBGS205 to Week 48 in Study MBGS206
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BGS649 0.1 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Femoral Neck) | -1.09 percentage of change | Standard Deviation 5.205 |
| BGS649 0.1 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Hip) | 0.01 percentage of change | Standard Deviation 3.407 |
| BGS649 0.1 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Lumbar Spine) | -1.94 percentage of change | Standard Deviation 3.378 |
| BGS649 0.3 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Femoral Neck) | -2.60 percentage of change | Standard Deviation 6.899 |
| BGS649 0.3 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Hip) | -1.71 percentage of change | Standard Deviation 3.59 |
| BGS649 0.3 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Lumbar Spine) | -3.31 percentage of change | Standard Deviation 5.301 |
| BGS649 1.0 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Hip) | 0.61 percentage of change | Standard Deviation 4.304 |
| BGS649 1.0 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Lumbar Spine) | -1.99 percentage of change | Standard Deviation 3.159 |
| BGS649 1.0 mg | Percentage Change From Baseline in DEXA Scan Density (g/cm^2) by Location for Subjects Randomised to Active Treatment in Study MBGS205 (Over-read) | Bone Density (Femoral Neck) | -0.15 percentage of change | Standard Deviation 5.155 |
Secondary
Percentage Change in Bone Alkaline Phosphatase
Percentage change in baseline in alkaline phosphatase from baseline in study MBGS205 to week 48 in MBGS206.
Time frame: 48 weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| BGS649 0.1 mg | Percentage Change in Bone Alkaline Phosphatase | 12.67 U/L | Standard Deviation 16.025 |
| BGS649 0.3 mg | Percentage Change in Bone Alkaline Phosphatase | 3.85 U/L | Standard Deviation 17.856 |
| BGS649 1.0 mg | Percentage Change in Bone Alkaline Phosphatase | 15.28 U/L | Standard Deviation 5.82 |
| Placebo to BGS649 0.1 mg | Percentage Change in Bone Alkaline Phosphatase | 14.46 U/L | Standard Deviation 22.493 |
| Placebo to BGS649 0.3 mg | Percentage Change in Bone Alkaline Phosphatase | -3.40 U/L | Standard Deviation 16.672 |
| Placebo to BGS649 1.0 mg | Percentage Change in Bone Alkaline Phosphatase | 3.80 U/L | Standard Deviation 13.025 |
Secondary
Percentage of Subjects Achieving Normalisation of Bioavailable (Total) Testosterone at Wk 48
Percentage of subjects where bioavailable testosterone was normalised at week 48 in Study MBGS206. Where normalisation was considered testosterone in the range 300-1000 mg/dL.
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGS649 0.1 mg | Percentage of Subjects Achieving Normalisation of Bioavailable (Total) Testosterone at Wk 48 | 25 Participants |
| BGS649 0.3 mg | Percentage of Subjects Achieving Normalisation of Bioavailable (Total) Testosterone at Wk 48 | 17 Participants |
| BGS649 1.0 mg | Percentage of Subjects Achieving Normalisation of Bioavailable (Total) Testosterone at Wk 48 | 19 Participants |
| Placebo to BGS649 0.1 mg | Percentage of Subjects Achieving Normalisation of Bioavailable (Total) Testosterone at Wk 48 | 6 Participants |
| Placebo to BGS649 0.3 mg | Percentage of Subjects Achieving Normalisation of Bioavailable (Total) Testosterone at Wk 48 | 11 Participants |
| Placebo to BGS649 1.0 mg | Percentage of Subjects Achieving Normalisation of Bioavailable (Total) Testosterone at Wk 48 | 5 Participants |
Secondary
Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location
Proportion of subjects with DEXA scan T- scores ≤ -2.5 at Week 48 in MBGS206 compared to baseline in MBGS205 by body location (using overread scan images).
Time frame: 48 Weeks
Population: The ITT population included all participants who: were randomised, and received at least 1 dose of study medication, and provided a Baseline lumbar spine BMD measure in MBGS205 and at least one available evaluation of lumbar spine post-Baseline in MBGS206. Here, the Overall Number of Participants Analyzed is the number of participants evaluable for this outcome measure and Number analyzed is the number of participants evaluated for each location.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| BGS649 0.1 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Femoral Neck) ≤ -2.5 | 0 Participants |
| BGS649 0.1 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Hip) ≤ -2.5 | 0 Participants |
| BGS649 0.1 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Lumbar Spine) ≤ -2.5 | 0 Participants |
| BGS649 0.3 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Femoral Neck) ≤ -2.5 | 0 Participants |
| BGS649 0.3 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Hip) ≤ -2.5 | 0 Participants |
| BGS649 0.3 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Lumbar Spine) ≤ -2.5 | 0 Participants |
| BGS649 1.0 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Femoral Neck) ≤ -2.5 | 0 Participants |
| BGS649 1.0 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Hip) ≤ -2.5 | 0 Participants |
| BGS649 1.0 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Lumbar Spine) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 0.1 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Femoral Neck) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 0.1 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Hip) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 0.1 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Lumbar Spine) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 0.3 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Femoral Neck) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 0.3 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Hip) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 0.3 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Lumbar Spine) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 1.0 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Hip) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 1.0 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Lumbar Spine) ≤ -2.5 | 0 Participants |
| Placebo to BGS649 1.0 mg | Percentage of Subjects With DEXA Scan T-score ≤ -2.5 at Week 48 by Location | T - Score (Femoral Neck) ≤ -2.5 | 0 Participants |