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| Name | Class |
|---|---|
| Novartis | INDUSTRY |
This study is designed as a 2-part study, with Part 1 being open-label to best determine the appropriate dose levels to use in Part 2, which has a randomized, double-blind, placebo controlled design. The study aims to assess the safety and tolerability of BGS649, and determine whether or not BGS649 is able to normalize testosterone levels and improve insulin sensitivity in obese, hypogonadotropic hypogonadal (OHH) men
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| BGS649 (Part 1) | Experimental | BGS649 1mg and 0.1mg in hard gelatin capsules. In part 1 there was individualised dosing to titrate the subject's testosterone into the normal range. If the dose was lower than 0.1mg then specific instructions for dilution of an oral solution of BGS649 were provided. |
|
| Placebo to BGS649 (Part 2) | Placebo Comparator | Matching placebo to BGS649 (0.3 and 0.1mg). 0.3mg placebo capsule given on Day 1 and 0.1mg placebo capsule on other treatment visits (week 1 to 11). |
|
| BGS649 (Part 2) | Experimental | 0.3 or 0.1mg hard gelatin capsules of BGS649 given orally. 0.3mg on Day 1 and 0.1 on all other treatment visits (week 1 to 11). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Investigational new drug company code: BGS649 | Drug |
| ||
| Placebo |
| Measure | Description | Time Frame |
|---|---|---|
| Percentage of Patients Achieving Normal Testosterone Levels | Percentage of patients achieving normal testosterone (2.50 - 9.50 ng/mL) levels at Week 4 and Week 12 | At Week 4 and 12 |
| Part 2: Change From Baseline at Homeostatic Model Assessment of Insulin Resistance (HOMA-IR & QUICKI Scores) at Week 4 and 12 | Pharmacodynamic change from baseline in HOMA-IR. Score at week 4 and week 12 as an assessment of insulin resistance. Low score representing high insulin sensitivity and a high score representing low insulin sensitivity or insulin resistance. HOMA-IR is a ration of Fasting insulin (mIU/L) : Fasting glucose (mmol). Pharmacodynamic change in QUICKI score at week 4 and week 12 as an assessment of insulin resistance. The QUICKI scale is a log score and a high score representing high insulin sensitivity and low score indicating low insulin sensitivity. Patients with a score below 0.3 are considered diabetic. Week 12 data is missing because there were inaccuracies in dosing of patients and so the study was terminated, only safety data was collected. | Baseline, Week 4 and Week 12 |
| Measure | Description | Time Frame |
|---|---|---|
| Part 2: Area Under the Concentration-time Curve From Time Zero to Time 't' (AUC0-168) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. The AUC 0-168 measures the amount of drug within the subjects blood over the 168h post-dosing at these timepoints. | 11 weeks |
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Inclusion Criteria:
Males who meet the criteria of obese, hypogonadotropic hypogonadism defined as:
Luteinizing hormone (LH) ≤ ULN
Follicle stimulating hormone (FSH) ≤ ULN
Estradiol within or above the normal range (defined as ≥ LLN of the approved assay)
Prolactin: within the normal range
Thyroid stimulating hormone (TSH): within the normal range
Ferritin: within the normal range
Patients agree to use a barrier method of contraception (e.g., condom), for the duration of the study and for at least 3 months following their Study Completion visit to prevent BGS649 exposure to their partners.
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jacqueline Parkin, PhD FRCP | Mereo BioPharma | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Novartis Investigative Site | Tucson | Arizona | 85712 | United States | ||
| Novartis Investigative Site |
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14 participants enrolled in Part 1 and 15 participants enrolled in part 2.
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| ID | Title | Description |
|---|---|---|
| FG000 | BGS649 Part 1 | BGS649 1mg and 0.1mg in hard gelatin capsules. In part 1 there was individualised dosing to titrate the subject's testosterone into the normal range. If the dose was lower than 0.1mg then specific instructions for dilution of an oral solution of BGS649 were provided. |
| FG001 | BGS649 Part 2 | BGS649 0.3mg hard gelatin capsule given orally on Day 1 and 0.1mg BGS649 capsule on other treatment visits (week 1 to 11). |
| FG002 | Placebo to BGS649 | Matching placebo to BGS649 (0.3 and 0.1mg). 0.3mg placebo capsule given on Day 1 and 0.1mg placebo capsule on other treatment visits (week 1 to 11). |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Part 1 |
| |||||||||||||
| Part 2 |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | BGS649 (Part 1) | BGS649 1mg and 0.1mg in hard gelatin capsules. In part 1 there was individualised dosing to titrate the subject's testosterone into the normal range. If the dose was lower than 0.1mg then specific instructions for dilution of an oral solution of BGS649 were provided. |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Age calculate from date of birth at time of consent |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Percentage of Patients Achieving Normal Testosterone Levels | Percentage of patients achieving normal testosterone (2.50 - 9.50 ng/mL) levels at Week 4 and Week 12 | Number/percentage of patients achieving normal sex hormone levels at Week 4 and Week 12 (Part 1 Only) | Posted | Count of Participants | Participants | At Week 4 and 12 |
|
|
16 weeks
Does not differ to clinicaltrials.gov. definitions
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | BGS649 (Part 1) Open Label | Individualised doses to titrate testosterone levels to within normal range. Doses ranged between 0.003mg and 5mg in total over the 11 week treatment period. For doses below 0.1mg, separate pharmacy instructions were provided to dilute an oral solution of BGS649. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Tongue neoplasm malignant stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Diarrhoea | Gastrointestinal disorders | Systematic Assessment |
Part 2 of the study was early terminated due to incorrect dosing, therefore only 8 of the 15 subjects enrolled completed 11 doses of treatment, and the remaining 7 subjects had incomplete dosing.
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Dr. Jackie Parkin | Mereo BioPharma | +44 333 0237300 | enquiries@mereobiopharma.com |
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| ID | Term |
|---|---|
| D009765 | Obesity |
| D007006 | Hypogonadism |
| ID | Term |
|---|---|
| D050177 | Overweight |
| D044343 | Overnutrition |
| D009748 | Nutrition Disorders |
| D009750 | Nutritional and Metabolic Diseases |
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Open-label in Part 1 and double-blind in Part 2.
| Drug |
|
| Part 2: Pharmacokinetics of BGS649: Maximum (Peak) Observed Blood Drug Concentration After Single Dose Administration (Cmax) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | Week 1 to Week 11 |
| Part 2: Pharmacokinetics of BGS649: Time to Reach Maximum (Peak) Blood Drug Concentration After Single Dose Administration (Tmax) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | Week 1 to Week 11 |
| PK of BGS649 Elimination Half-life Associated With the Terminal Slope of a Semi Logarithmic Concentration-time Curve (T1/2) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | Week 1 to Week 11 |
| San Diego |
| California |
| 92120 |
| United States |
| Novartis Investigative Site | Miramar | Florida | 33025 | United States |
| Novartis Investigative Site | West Valley City | Utah | 84120 | United States |
| Novartis Investigative Site | Montreal | Quebec | H3X 2H9 | Canada |
| NOT COMPLETED |
|
| BGS649 (Part 2) |
BGS649 0.3mg hard gelatin capsule given orally on Day 1 and 0.1mg BGS649 capsule on other treatment visits (week 1 to 11). |
| BG002 | Placebo to BGS649 (Part 2) | Matching placebo to BGS649 (0.3 and 0.1mg). 0.3mg placebo capsule given on Day 1 and 0.1mg placebo capsule on other treatment visits (week 1 to 11). |
| BG003 | Total | Total of all reporting groups |
Part 1 and Part 2 results were analysed completed separately throughout the study
| Mean |
| Standard Deviation |
| years |
|
| Sex: Female, Male | Part 1 and Part 2 patients were analysed completed separately throughout the study | Count of Participants | Participants |
|
| Race/Ethnicity, Customized | Part 1 and Part 2 of the study were reported/analysed separately and so combined totals are not available | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| Body Mass Index | Body Mass index calculated | Part A and Part B were analysed and reported separately in the study | Mean | Standard Deviation | kg/m2 |
|
| Counts |
|---|
| Participants |
|
|
| Primary | Part 2: Change From Baseline at Homeostatic Model Assessment of Insulin Resistance (HOMA-IR & QUICKI Scores) at Week 4 and 12 | Pharmacodynamic change from baseline in HOMA-IR. Score at week 4 and week 12 as an assessment of insulin resistance. Low score representing high insulin sensitivity and a high score representing low insulin sensitivity or insulin resistance. HOMA-IR is a ration of Fasting insulin (mIU/L) : Fasting glucose (mmol). Pharmacodynamic change in QUICKI score at week 4 and week 12 as an assessment of insulin resistance. The QUICKI scale is a log score and a high score representing high insulin sensitivity and low score indicating low insulin sensitivity. Patients with a score below 0.3 are considered diabetic. Week 12 data is missing because there were inaccuracies in dosing of patients and so the study was terminated, only safety data was collected. | Could not be analysed due to drug administration errors. Week 12 data is missing because they were inaccuracies in the dosing of patients and so the study was terminated early and efficacy data not reported for the affected patients. | Posted | Geometric Mean | 95% Confidence Interval | units on a scale | Baseline, Week 4 and Week 12 |
|
|
|
| Secondary | Part 2: Area Under the Concentration-time Curve From Time Zero to Time 't' (AUC0-168) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. The AUC 0-168 measures the amount of drug within the subjects blood over the 168h post-dosing at these timepoints. | PK Analysis Set included 7 patients given BGS649 in Part 2. | Posted | Mean | Standard Deviation | ng*hr/mL | 11 weeks |
|
|
|
| Secondary | Part 2: Pharmacokinetics of BGS649: Maximum (Peak) Observed Blood Drug Concentration After Single Dose Administration (Cmax) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | PK Analysis Set | Posted | Mean | Standard Deviation | ng/mL | Week 1 to Week 11 |
|
|
|
| Secondary | Part 2: Pharmacokinetics of BGS649: Time to Reach Maximum (Peak) Blood Drug Concentration After Single Dose Administration (Tmax) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | PK Population | Posted | Mean | Standard Deviation | hours | Week 1 to Week 11 |
|
|
|
| Secondary | PK of BGS649 Elimination Half-life Associated With the Terminal Slope of a Semi Logarithmic Concentration-time Curve (T1/2) | PK sampling was performed at 0hr (pre-dose), 1 hr, 8 hr, 24 hr, 72 hr, and 168 hr on the following occasions Week 1, Week 4 and week 11. | PK Analysis Set. Sparse PK sampling (4 samples over 672 h) was included for the PK profile for Week 4; Cmax was included in λz estimation, therefore T1/2 was not reported for all profiles in Week 4. | Posted | Mean | Standard Deviation | hours | Week 1 to Week 11 |
|
|
|
| 0 |
| 14 |
| 11 |
| 14 |
| EG001 | BGS649 (Part 2) | All subjects were given 0.3mg on Day 1 and then 0.1mg on all other dosing visits (weeks 2-11). | 0 | 7 | 5 | 7 |
| EG002 | Placebo to BGS649 (Part 2) | Matching placebo capsules on Day 1 and all other dosing visits (weeks 2-11). | 1 | 8 | 7 | 8 |
| Pulmonary embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Frequent bowel movements | Gastrointestinal disorders | Systematic Assessment |
|
| Headache | Nervous system disorders | Systematic Assessment |
|
| Dizziness | Nervous system disorders | Systematic Assessment |
|
| Arthralgia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Spontaneous penile erection | Reproductive system and breast disorders | Systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Oropharyngeal pain | Reproductive system and breast disorders | Systematic Assessment |
|
| Cough | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Amnesia | Nervous system disorders | Systematic Assessment |
|
| Asthenia | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Blood triglycerides increased | Investigations | Systematic Assessment |
|
| Diverticulitis | Gastrointestinal disorders | Systematic Assessment |
|
| Ecchymosis | Skin and subcutaneous tissue disorders | Systematic Assessment |
|
| Increased appetitie | Metabolism and nutrition disorders | Systematic Assessment |
|
| Libido increased | Reproductive system and breast disorders | Systematic Assessment |
|
| Musculoskeletal pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | Systematic Assessment |
|
| Night sweats | Nervous system disorders | Systematic Assessment |
|
| Nocturia | Renal and urinary disorders | Systematic Assessment |
|
| Pain | General disorders | Systematic Assessment |
|
| Pulmonary Embolism | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Pyrexia | Nervous system disorders | Systematic Assessment |
|
| Somnolence | Nervous system disorders | Systematic Assessment |
|
| Stress | Nervous system disorders | Systematic Assessment |
|
| Terminal insomnia | Nervous system disorders | Systematic Assessment |
|
| Thrombosis | Blood and lymphatic system disorders | Systematic Assessment |
|
| Tongue neoplasm malignant stage unspecified | Neoplasms benign, malignant and unspecified (incl cysts and polyps) | Systematic Assessment |
|
| Upper respiratory tract infection | Respiratory, thoracic and mediastinal disorders | Systematic Assessment |
|
| Vaccination site pain | General disorders | Systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | Systematic Assessment |
|
All PIs must seek written permission from the sponsor prior to publication of any trial results.
| D001835 |
| Body Weight |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |
| D006058 | Gonadal Disorders |
| D004700 | Endocrine System Diseases |
| Title | Measurements |
|---|---|
|
| Title | Measurements |
|---|---|
| Female |
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| Male |
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| Native American |
|
| Title | Measurements |
|---|---|
| Caucasian |
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| Black |
|
| Native American |
|
| Title | Measurements |
|---|---|
|
| QUICKI at 4 weeks |
|
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| HOMA-IR at 12 weeks |
|
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| Week 11 |
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| Week 11 |
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| Week 11 |
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| Week 11 |
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