Endometriosis
Conditions
Keywords
Endometriosis, Infertility, Pain, Vaginal Diseases, Uterine Diseases
Brief summary
This study will assess the safety and tolerability of BGS649 in women with moderate to severe endometriosis.
Interventions
DRUGActive treatment with a high dose of BGS649
DRUGActive treatment with a low dose of BGS649
DRUGPlacebo treatment to blind study
Sponsors
Novartis
Mereo BioPharma
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 40 Years
Healthy volunteers
No
Inclusion criteria
* Premenopausal women with documented moderate to severe endometriosis. Occurrence of three sequential menstrual cycles of 24-35 days duration prior to enrollment. * Laparoscopically proven diagnosis of moderate to severe endometriosis (diagnosed within the past 10 years before screening). * Patients not planning to become pregnant within one year after the screening visit and willing to use two effective methods of non-hormonal, barrier birth control for the duration of the study or who are surgically sterile. * Patients must have a score of at least 4 on the numerical rating scale (NRS) for one of the following three pain measurements: pelvic pain, menstrual pain and dyspareunia
Exclusion criteria
* Estrogen replacement therapy using either prescription medications or estrogen-containing OTC nutritional/herbal supplements such as soy extracts or topical estrogens. * Aromatase inhibitor therapy (includes Femara (letrozole), Aromasin (exemestane) or Arimidex (anastrozole) within the past 12 months. * Oral bisphosphonate therapy (i.e. Fosamax (alendronate)) within the past 6 months or intravenous bisphosphonate (i.e., Reclast, pamidronate) \< 15 months from screening. * Systemic glucocorticoid therapy within the past 4 weeks. * Contra-indications to oral contraceptive use. Other protocol-defined inclusion/
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Develop 2 or More Follicles With Diameter 16 mm or Larger | 8 months | Proportion of patients who develop 2 or more follicles with diameter 16 mm or larger. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic Profille of BGS649 as Described by AUC0-672h | 8 hours | AUC0-672 is a measurement of how much drug reaches a person's bloodstream in a given period of time after a dose is given. Measurements were performed at dose 1 (in cycle 2) and after dose 2 (in cycle 4). Sampling occured at pre-dose, 0.5-1.5h and 4-8 h post-dose. |
| Pharmacokinetic Profile of BGS649 as Described by Cmax | 8 hours | The peak plasma concentration of BGS649 after dosing at cycle 2 and cycle 4. Measurements were performed at dose 1 (in cycle 2) and after dose 2 (in cycle 4). Sampling occured at pre-dose, 0.5-1.5h and 4-8 h post-dose. |
| Pharmacokinetic Profile of BGS649 as Described by Tmax | 8 hours | Time taken to reach the maximum concentration in plasma of BGS649 at cycle 2 and cycle 4. Measurements were performed at dose 1 (in cycle 2) and after dose 2 (in cycle 4). Sampling occurred at pre-dose, 0.5-1.5h and 4-8 h post-dose. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| BGS649 High Dose 1 BGS649 1.0mg capsule with three 0.1 mg placebo capsules | 2 |
| BGS649 Low Dose 1 BGS649 1.0 mg placebo capsule and 3 BGS649 0.1 mg capsules | 2 |
| Placebo 1 matching placebo 1.0mg matching and three matching 0.1 mg placebo capsules | 2 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 |
|---|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 0 | 1 |
Baseline characteristics
| Characteristic | Total | BGS649 High Dose | BGS649 Low Dose | Placebo |
|---|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Age, Continuous | 29 years | 30 years | 28 years | 30.5 years |
| Race/Ethnicity, Customized Black | 1 Participants | 1 Participants | 0 Participants | 0 Participants |
| Race/Ethnicity, Customized Caucasian | 5 Participants | 1 Participants | 2 Participants | 2 Participants |
| Region of Enrollment United States | 6 participants | 2 participants | 2 participants | 2 participants |
| Sex: Female, Male Female | 6 Participants | 2 Participants | 2 Participants | 2 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — | — / — |
| other Total, other adverse events | 2 / 2 | 2 / 2 | 2 / 2 |
| serious Total, serious adverse events | 0 / 2 | 0 / 2 | 0 / 2 |
Outcome results
Primary
Proportion of Patients Who Develop 2 or More Follicles With Diameter 16 mm or Larger
Proportion of patients who develop 2 or more follicles with diameter 16 mm or larger.
Time frame: 8 months
Population: Proportion of patients who develop 2 or more follicles with diameter 16 mm or larger
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| BGS649 High Dose | Proportion of Patients Who Develop 2 or More Follicles With Diameter 16 mm or Larger | 2 Participants |
| BGS649 Low Dose | Proportion of Patients Who Develop 2 or More Follicles With Diameter 16 mm or Larger | 2 Participants |
| Placebo | Proportion of Patients Who Develop 2 or More Follicles With Diameter 16 mm or Larger | 0 Participants |
Secondary
Pharmacokinetic Profile of BGS649 as Described by Cmax
The peak plasma concentration of BGS649 after dosing at cycle 2 and cycle 4. Measurements were performed at dose 1 (in cycle 2) and after dose 2 (in cycle 4). Sampling occured at pre-dose, 0.5-1.5h and 4-8 h post-dose.
Time frame: 8 hours
Population: Pharmacokinetic patient population. Study met the pre-defined safety stopping criteria and so was not fully enrolled. The PK results of for one of the patients could not be reported - missing data for cycle 2 and meeting the stopping criteria before cycle 4.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| BGS649 High Dose | Pharmacokinetic Profile of BGS649 as Described by Cmax | Cycle 2 | 9.040 ng/mL | Standard Deviation 4.0447 |
| BGS649 High Dose | Pharmacokinetic Profile of BGS649 as Described by Cmax | Cycle 4 | 15.25 ng/mL | Standard Deviation 0.91924 |
| BGS649 Low Dose | Pharmacokinetic Profile of BGS649 as Described by Cmax | Cycle 2 | 2.720 ng/mL | — |
| BGS649 Low Dose | Pharmacokinetic Profile of BGS649 as Described by Cmax | Cycle 4 | 3.410 ng/mL | — |
Secondary
Pharmacokinetic Profile of BGS649 as Described by Tmax
Time taken to reach the maximum concentration in plasma of BGS649 at cycle 2 and cycle 4. Measurements were performed at dose 1 (in cycle 2) and after dose 2 (in cycle 4). Sampling occurred at pre-dose, 0.5-1.5h and 4-8 h post-dose.
Time frame: 8 hours
Population: Pharmacokinetic patient population. Study met the pre-defined safety stopping criteria and so was not fully enrolled. The PK results of for one of the patients could not be reported - missing data for cycle 2 and meeting the stopping criteria before cycle 4.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| BGS649 High Dose | Pharmacokinetic Profile of BGS649 as Described by Tmax | Cycle 2 | 1.00 hours |
| BGS649 High Dose | Pharmacokinetic Profile of BGS649 as Described by Tmax | Cycle 4 | 1.00 hours |
| BGS649 Low Dose | Pharmacokinetic Profile of BGS649 as Described by Tmax | Cycle 2 | 1.00 hours |
| BGS649 Low Dose | Pharmacokinetic Profile of BGS649 as Described by Tmax | Cycle 4 | 1.00 hours |
Secondary
Pharmacokinetic Profille of BGS649 as Described by AUC0-672h
AUC0-672 is a measurement of how much drug reaches a person's bloodstream in a given period of time after a dose is given. Measurements were performed at dose 1 (in cycle 2) and after dose 2 (in cycle 4). Sampling occured at pre-dose, 0.5-1.5h and 4-8 h post-dose.
Time frame: 8 hours
Population: Full analysis set
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| BGS649 High Dose | Pharmacokinetic Profille of BGS649 as Described by AUC0-672h | AUC0-672 at Cycle 2 | 2557 ng*hr/mL |
| BGS649 High Dose | Pharmacokinetic Profille of BGS649 as Described by AUC0-672h | AUC0-672 at Cycle 4 | 3283 ng*hr/mL |
| BGS649 Low Dose | Pharmacokinetic Profille of BGS649 as Described by AUC0-672h | AUC0-672 at Cycle 2 | 443.8 ng*hr/mL |
| BGS649 Low Dose | Pharmacokinetic Profille of BGS649 as Described by AUC0-672h | AUC0-672 at Cycle 4 | 639.6 ng*hr/mL |