BGS649 Monotherapy in Moderate to Severe Endometriosis Patients

• Sponsor: Mereo BioPharma (Industry)
• Overall Status: Completed
• CT.gov ID: NCT01190475
• Collaborator: Novartis (Industry)
• Enrollment: 6
• Location: 1
• Arms: 3
• Duration (Months): 14
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This study will assess the safety and tolerability of BGS649 in women with moderate to severe endometriosis.

Condition or Disease	Intervention/Treatment	Phase
Endometriosis	Drug: Active treatment with a high dose of BGS649; Drug: Active treatment with a low dose of BGS649; Drug: Placebo treatment to blind study	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 6 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: A Randomized, Double-blind, Double-dummy, Placebo-controlled Study of Oral BGS649 Monotherapy Assessing Safety and Tolerability in Patients With Moderate to Severe Endometriosis
• Study Start Date: Jul 1, 2010
• Actual Primary Completion Date: Sep 1, 2011
• Actual Study Completion Date: Sep 1, 2011

Arms and Interventions

Arm	Intervention/Treatment
Experimental: BGS649 high dose 1 BGS649 1.0mg capsule with three 0.1 mg placebo capsules.	Drug: Active treatment with a high dose of BGS649
Experimental: BGS649 low dose 1 BGS649 1.0 mg placebo capsule and 3 BGS649 0.1 mg capsules	Drug: Active treatment with a low dose of BGS649
Placebo Comparator: Placebo to BGS649 1 matching placebo 1.0mg matching and three matching 0.1 mg placebo capsules	Drug: Placebo treatment to blind study

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 40 Years
• Sexes Eligible for Study: Female
• Accepts 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/exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novartis Investigative Site	Anaheim	California	United States	92801

Sponsors and Collaborators

• Mereo BioPharma
• Novartis

Investigators

• Study Director: Jacqueline Parkin, PhD FRCP, Mereo BioPharma

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Mereo BioPharma
• ClinicalTrials.gov Identifier: NCT01190475
• Other Study ID Numbers: CBGS649A2105
• First Posted: Aug 27, 2010
• Last Update Posted: Oct 27, 2020
• Last Verified: Oct 1, 2020

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Keywords provided by Mereo BioPharma: Endometriosis; Infertility; Pain; Vaginal Diseases; Uterine Diseases
• Additional relevant MeSH terms: Endometriosis

Study Results

Participant Flow

Arm/Group Title	BGS649 High Dose	BGS649 Low Dose	Placebo
Arm/Group Description	1 BGS649 1.0mg capsule with three 0.1 mg placebo capsules	1 BGS649 1.0 mg placebo capsule and 3 BGS649 0.1 mg capsules	1 matching placebo 1.0mg matching and three matching 0.1 mg placebo capsules
Period Title: Overall Study
STARTED	2	2	2
COMPLETED	2	2	1
NOT COMPLETED	0	0	1

Baseline Characteristics

Arm/Group Title	BGS649 High Dose	BGS649 Low Dose	Placebo	Total
Arm/Group Description	1 BGS649 1.0mg capsule with three 0.1 mg placebo capsules	1 BGS649 1.0 mg placebo capsule and 3 BGS649 0.1 mg capsules	1 matching placebo 1.0mg matching and three matching 0.1 mg placebo capsules	Total of all reporting groups
Overall Participants	2	2	2	6
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%	0 0%
Between 18 and 65 years	2 100%	2 100%	2 100%	6 100%
>=65 years	0 0%	0 0%	0 0%	0 0%
Age (years) [Mean (Full Range) ]
Mean (Full Range) [years]	30	28	30.5	29
Sex: Female, Male (Count of Participants)
Female	2 100%	2 100%	2 100%	6 100%
Male	0 0%	0 0%	0 0%	0 0%
Race/Ethnicity, Customized (Count of Participants)
Caucasian	1 50%	2 100%	2 100%	5 83.3%
Black	1 50%	0 0%	0 0%	1 16.7%
Region of Enrollment (participants) [Number]
United States	2 100%	2 100%	2 100%	6 100%

Outcome Measures

1. Primary Outcome

Title	Proportion of Patients Who Develop 2 or More Follicles With Diameter 16 mm or Larger
Description	Proportion of patients who develop 2 or more follicles with diameter 16 mm or larger.
Time Frame	8 months

Outcome Measure Data

Analysis Population Description

Proportion of patients who develop 2 or more follicles with diameter 16 mm or larger

Arm/Group Title	BGS649 High Dose	BGS649 Low Dose	Placebo
Arm/Group Description	BGS649	BGS649	Placebo
Measure Participants	2	2	2
Count of Participants [Participants]	2 100%	2 100%	0 0%

2. Secondary Outcome

Title	Pharmacokinetic Profille of BGS649 as Described by AUC0-672h
Description	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

Outcome Measure Data

Analysis Population Description

Full analysis set

Arm/Group Title	BGS649 High Dose	BGS649 Low Dose
Arm/Group Description	1 BGS649 1.0mg capsule with three 0.1 mg placebo capsules. Active treatment with a high dose of BGS649	1 BGS649 1.0 mg placebo capsule and 3 BGS649 0.1 mg capsules Active treatment with a low dose of BGS649
Measure Participants	2	2
AUC0-672 at Cycle 2	2557	443.8
AUC0-672 at Cycle 4	3283	639.6

3. Secondary Outcome

Title	Pharmacokinetic Profile of BGS649 as Described by Cmax
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	BGS649 High Dose	BGS649 Low Dose
Arm/Group Description	1 BGS649 1.0mg capsule with three 0.1 mg placebo capsules. Active treatment with a high dose of BGS649	1 BGS649 1.0 mg placebo capsule and 3 BGS649 0.1 mg capsules Active treatment with a low dose of BGS649
Measure Participants	2	1
Cycle 2	9.040 (4.0447)	2.720
Cycle 4	15.25 (0.91924)	3.410

4. Secondary Outcome

Title	Pharmacokinetic Profile of BGS649 as Described by Tmax
Description	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

Outcome Measure Data

Analysis Population Description

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/Group Title	BGS649 High Dose	BGS649 Low Dose
Arm/Group Description	1 BGS649 1.0mg capsule with three 0.1 mg placebo capsules. Active treatment with a high dose of BGS649	1 BGS649 1.0 mg placebo capsule and 3 BGS649 0.1 mg capsules Active treatment with a low dose of BGS649
Measure Participants	2	1
Cycle 2	1.00	1.00
Cycle 4	1.00	1.00

Adverse Events

Arm/Group Title	BGS649 High Dose		BGS649 Low Dose		Placebo
Arm/Group Description	1 BGS649 1.0mg capsule with three 0.1 mg placebo capsules.		1 BGS649 1.0 mg placebo capsule and 3 BGS649 0.1 mg capsules		1 matching placebo 1.0mg matching and three matching 0.1 mg placebo capsules
All Cause Mortality
	BGS649 High Dose		BGS649 Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	BGS649 High Dose		BGS649 Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/2 (0%)		0/2 (0%)		0/2 (0%)
Other (Not Including Serious) Adverse Events
	BGS649 High Dose		BGS649 Low Dose		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	2/2 (100%)		2/2 (100%)		2/2 (100%)
Gastrointestinal disorders
Abdominal pain	0/2 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Nausea	1/2 (50%)	1	0/2 (0%)	0	0/2 (0%)	0
Nervous system disorders
Headache	0/2 (0%)	0	0/2 (0%)	0	1/2 (50%)	1
Reproductive system and breast disorders
Menorrhagia	0/2 (0%)	0	1/2 (50%)	1	0/2 (0%)	0
Metrorrhagia	1/2 (50%)	1	0/2 (0%)	0	0/2 (0%)	0
Respiratory, thoracic and mediastinal disorders
Bronchitis	0/2 (0%)	0	0/2 (0%)	0	1/2 (50%)	1
Upper respiratory tract infection	1/2 (50%)	1	0/2 (0%)	0	0/2 (0%)	0
Skin and subcutaneous tissue disorders
Acne	0/2 (0%)	0	0/2 (0%)	0	1/2 (50%)	1

Limitations/Caveats

The study was prematurely terminated because the safety endpoint was reached after a total of 6 patients were randomized into one of the 3 treatment arms.

More Information

Certain Agreements

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

All PIs must seek written permission from the sponsor prior to publication of any trial results.