Crossover Study of the Safety and PK Properties of Proellex®

• Sponsor: Repros Therapeutics Inc. (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00749879
• Collaborator: (none)
• Enrollment: 17
• Location: 1
• Arms: 5
• Actual Duration (Months): 2.4
• Patients Per Site Per Month: 7.1

Study Details

Study Description

Brief Summary

Study to evaluate the PK of 25 mg and 50 mg of Proellex from 2 different suppliers in the fed and fasting states.

Condition or Disease	Intervention/Treatment	Phase
Pharmacokinetics	Drug: Proellex	Phase 1

Detailed Description

This study is intended to evaluate the pharmacokinetic properties of two doses (25 mg and 50 mg) of Proellex® formulated with microcrystalline cellulose (MCC) from 2 different suppliers in the fed and fasting states.

Study Design

• Study Type: Interventional
• Actual Enrollment: 17 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Basic Science
• Official Title: A Phase I, Open-Label, Randomized, Single-Center, Unblinded, Single-Dose, Five-Way Crossover Study of the Safety and PK Properties of Proellex®
• Actual Study Start Date: Aug 11, 2008
• Actual Primary Completion Date: Oct 23, 2008
• Actual Study Completion Date: Oct 23, 2008

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 25 mg AMCC fed 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State	Drug: Proellex; 25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting; Other Names: Telapristone acetate
Experimental: 25 mg AMCC fasting 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State	Drug: Proellex; 25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting; Other Names: Telapristone acetate
Experimental: 50 mg AMCC fed 2, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State	Drug: Proellex; 25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting; Other Names: Telapristone acetate
Experimental: 50 mg AMCC fasting 2, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State	Drug: Proellex; 25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting; Other Names: Telapristone acetate
Experimental: 50 mg SMCC fasting 2, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State	Drug: Proellex; 25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting; Other Names: Telapristone acetate

Outcome Measures

Primary Outcome Measures

1. Cmax of Proellex [Up to 72 hours post-dose]

   Maximum observed concentration of Proellex

2. AUC0-last of Proellex [Up to 72 hours post dose]

   Area under the plasma concentration curve from time 0 to the last measurable plasma concentration time point, up to 72 hours.

3. Tmax of Proellex [Up to 72 hours post dose]

   Time to maximum plasma occurrence of Cmax

4. AUC0-infinity of Proellex [Up to 72 hours post dose]

   Area under the plasma concentration curve from time 0 to extrapolated to infinity, calculated by summing the area under the curve from time zero to the time of the last quantifiable concentration

5. Terminal Elimination Half-life (T1/2) of Proellex [Up to 72 hours post dose]

   Time to maximum plasma occurrence of T1/2, calculated as ln(2)/Elimination rate constant.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 34 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Subject must be able to speak, read, and understand English and be willing and able to provide written informed consent in English on an Institutional Review Board (IRB)

• Premenopausal women aged 18-34, inclusive, with body mass index between 18 and 35, inclusive

• Women of child-bearing potential must be willing to use effective non-hormonal, double-barrier method contraception during the study period and for a minimum of 30 days after discontinuation of the study medication. Women who have had a hysterectomy will be allowed into the study

• Must have a negative urine pregnancy test at screening

• Able to swallow gelatin capsules

• Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the Principal Investigator that would interfere with the subject participating this study

• Must have agreed to not attempt to become pregnant at any time during study participation or for 30 days thereafter

• Other inclusion criteria may apply

Exclusion Criteria:

• Symptomatic uterine fibroids or endometriosis

• Past or present history of any significant cardiovascular, renal, or hepatic disease requiring ongoing medical therapy or clinical intervention

• Past or present history of thrombophlebitis, thromboembolic disorders, or cerebrovascular accident

• Abnormal screening visit vital signs or clinical laboratory evaluation considered clinically significant by the Principal Investigator

• Significant organ abnormality or disease (based on the Principal Investigator's judgment) that would in the opinion of the Principal Investigator exclude the subject from participating

• Other exclusion criteria may apply

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Healthcare Discoveries Inc.	San Antonio	Texas	United States	78229

Sponsors and Collaborators

• Repros Therapeutics Inc.

Investigators

• Study Director: Anna Chan, Allergan

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Repros Therapeutics Inc.
• ClinicalTrials.gov Identifier: NCT00749879
• Other Study ID Numbers: ZP-008
• First Posted: Sep 9, 2008
• Last Update Posted: Apr 29, 2019
• Last Verified: Jan 1, 2019

• Keywords provided by Repros Therapeutics Inc.: PK; Pharmacokinetics

Study Results

Participant Flow

Recruitment Details	Of the 17 participants, 4 did not meet inclusion/exclusion criteria, and 1 participant enrolled as a spare was not needed, resulting in their involvement in the study being terminated. The remaining 12 participants completed all five study treatments of Proellex.
Pre-assignment Detail	Each of the 12 participants were randomly assigned a unique sequence of the following 5 following open-label treatments of Proellex 25 mg formulated with AMCC (fed state) 25 mg formulated with AMCC (fasting state) 50 mg formulated with AMCC (fed state) 50 mg formulated with AMCC (fasting state) 50 mg formulated with SMCC (fasting state)

Arm/Group Title	Proellex
Arm/Group Description	in randomly assigned sequences, all study participants received 5 open-label treatments of Proellex: 25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State Proellex; 25 mg capsule administered once orally after subjects have been fed; 25 mg capsule administered once orally while subjects are fasting; 2, 25 mg capsules administered once orally after subjects have been fed; 2, 25 mg capsules administered once orally while subjects are fasting; and 2, 25 mg capsules administered once orally while subjects are fasting
Period Title: Overall Study
STARTED	12
COMPLETED	12
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	All Subjects
Arm/Group Description	All subjects enrolled
Overall Participants	12
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 100%
>=65 years	0 0%
Sex: Female, Male (Count of Participants)
Female	12 100%
Male	0 0%
Region of Enrollment (Count of Participants)
United States	12 100%

Outcome Measures

1. Primary Outcome

Title	Cmax of Proellex
Description	Maximum observed concentration of Proellex
Time Frame	Up to 72 hours post-dose

Outcome Measure Data

Analysis Population Description

12 subjects received all 5 treatments

Arm/Group Title	25 mg AMCC Fed	25 mg AMCC Fasting	50 mg AMCC Fed	50 mg AMCC Fasting	50 mg SMCC Fasting
Arm/Group Description	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State
Measure Participants	12	12	12	12	12
Mean (Standard Deviation) [ng/mL]	485.6 (151.3)	876.7 (201.9)	912.9 (157.6)	1322.5 (154.5)	1346.7 (148.5)

2. Primary Outcome

Title	AUC0-last of Proellex
Description	Area under the plasma concentration curve from time 0 to the last measurable plasma concentration time point, up to 72 hours.
Time Frame	Up to 72 hours post dose

Outcome Measure Data

Analysis Population Description

All 12 subjects received each treatment

Arm/Group Title	25 mg AMCC Fed	25 mg AMCC Fasting	50 mg AMCC Fed	50 mg AMCC Fasting	50 mg SMCC Fasting
Arm/Group Description	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State
Measure Participants	12	12	12	12	12
Mean (Standard Deviation) [ng/mL*hour]	6142.1 (2845.9)	5765.7 (3036.6)	11094.2 (4209.0)	9252.0 (4217.5)	9576.2 (4328.3)

3. Primary Outcome

Title	Tmax of Proellex
Description	Time to maximum plasma occurrence of Cmax
Time Frame	Up to 72 hours post dose

Outcome Measure Data

Analysis Population Description

All 12 subjects received each treatment

Arm/Group Title	25 mg AMCC Fed	25 mg AMCC Fasting	50 mg AMCC Fed	50 mg AMCC Fasting	50 mg SMCC Fasting
Arm/Group Description	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State
Measure Participants	12	12	12	12	12
Mean (Standard Deviation) [Hours]	2.6 (0.6)	0.8 (0.2)	2.6 (1.0)	0.9 (0.4)	0.7 (0.2)

4. Primary Outcome

Title	AUC0-infinity of Proellex
Description	Area under the plasma concentration curve from time 0 to extrapolated to infinity, calculated by summing the area under the curve from time zero to the time of the last quantifiable concentration
Time Frame	Up to 72 hours post dose

Outcome Measure Data

Analysis Population Description

All 12 subjects received each treatment

Arm/Group Title	25 mg AMCC Fed	25 mg AMCC Fasting	50 mg AMCC Fed	50 mg AMCC Fasting	50 mg SMCC Fasting
Arm/Group Description	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State
Measure Participants	12	12	12	12	12
Mean (Standard Deviation) [ng/mL*hour]	7039.8 (3715.6)	6897.0 (4440.7)	13014.9 (6753.2)	11271.6 (6726.6)	11804.8 (7186.9)

5. Primary Outcome

Title	Terminal Elimination Half-life (T1/2) of Proellex
Description	Time to maximum plasma occurrence of T1/2, calculated as ln(2)/Elimination rate constant.
Time Frame	Up to 72 hours post dose

Outcome Measure Data

Analysis Population Description

All 12 subjects received each treatment

Arm/Group Title	25 mg AMCC Fed	25 mg AMCC Fasting	50 mg AMCC Fed	50 mg AMCC Fasting	50 mg SMCC Fasting
Arm/Group Description	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State	Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State	Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State
Measure Participants	12	12	12	12	12
Mean (Standard Deviation) [Hours]	22.1 (8.2)	25.2 (10.4)	23.8 (10.8)	26.7 (11.8)	27.5 (11.9)

Adverse Events

Arm/Group Title	25 mg AMCC Fed		25 mg AMCC Fasting		50 mg AMCC Fed		50 mg AMCC Fasting		50 mg SMCC Fasting
Arm/Group Description	25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fed State		25 mg Proellex capsule formulated with AMCC coarse microcrystalline cellulose Fasting State		Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fed State		Two, 25 mg Proellex capsules formulated with AMCC coarse microcrystalline cellulose Fasting State		Two, 25 mg Proellex capsules formulated with SMCC microcrystalline cellulose Fasting State
All Cause Mortality
	25 mg AMCC Fed		25 mg AMCC Fasting		50 mg AMCC Fed		50 mg AMCC Fasting		50 mg SMCC Fasting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	25 mg AMCC Fed		25 mg AMCC Fasting		50 mg AMCC Fed		50 mg AMCC Fasting		50 mg SMCC Fasting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)		0/12 (0%)
Other (Not Including Serious) Adverse Events
	25 mg AMCC Fed		25 mg AMCC Fasting		50 mg AMCC Fed		50 mg AMCC Fasting		50 mg SMCC Fasting
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	1/12 (8.3%)		2/12 (16.7%)		4/12 (33.3%)		7/12 (58.3%)		5/12 (41.7%)
Cardiac disorders
Palpitations	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Tachycardia	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Gastrointestinal disorders
Nausea	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Abdominal pain	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1
Metabolism and nutrition disorders
Hyperkalemia	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0
Nervous system disorders
Presyncope	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Dizziness	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0
Headache	1/12 (8.3%)	1	0/12 (0%)	0	1/12 (8.3%)	1	1/12 (8.3%)	1	2/12 (16.7%)	2
Reproductive system and breast disorders
Pelvi pain NOS	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Nipple pain	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1	0/12 (0%)	0	0/12 (0%)	0
Oligomenorrhea	0/12 (0%)	0	1/12 (8.3%)	1	3/12 (25%)	3	3/12 (25%)	3	2/12 (16.7%)	2
Respiratory, thoracic and mediastinal disorders
Rhinitis allergic	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	0/12 (0%)	0	1/12 (8.3%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

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

Prior to publication, Investigator shall submit to the Sponsor a copy of any proposed publication. Sponsor shall have sixty (60) days to review the proposed publication for possible disclosure of Sponsor's Confidential Information and, upon request of Sponsor, Investigator shall delete any of Sponsor's Confidential Information or withhold submission of such publication to allow Sponsor to protect its intellectual property rights