Open-Label, Multiple-Dose, Non-Randomized Study to Assess Drug-Drug Interactions of Proellex® in Female Subjects

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Repros Therapeutics Inc.
ClinicalTrials.gov Identifier:
NCT00741468
First received: August 25, 2008
Last updated: August 20, 2014
Last verified: August 2014
  Purpose

This study will assess possible drug-drug interactions with specific isoenzymes over a total study duration of 6-8 weeks. Blood samples collected pre and post-dose, and urine samples collected post dose will be analyzed.


Condition Intervention Phase
Drug Interactions
Drug: Proellex
Drug: CYP1A2 probe
Drug: CYP2C9 probe
Drug: CYP2C19 probe
Drug: CYP2D6 probe
Drug: CYP3A4 probe
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacodynamics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Multiple-Dose, Non-Randomized Study to Assess the Drug-Drug Interactions of Proellex® (CDB-4124) With Cytochrome P450 Isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in Healthy Female Subjects

Resource links provided by NLM:


Further study details as provided by Repros Therapeutics Inc.:

Primary Outcome Measures:
  • Plasma AUC Ratio of Day 1 and Day 8 [ Time Frame: 8 days ] [ Designated as safety issue: Yes ]

    Assessment of the drug-drug interactions of Proellex® (CDB-4124) with cytochrome P450 isoenzymes CYP1A2, 2C9, 2C19, 2D6, and 3A4 in healthy female subjects administered 50 mg Proellex® once daily (QD). The Day 8 AUC was compared to the Day 1 AUC to determine inhibition.

    For CYP1A2 the plasma paraxanthine/caffeine MR ratio (metabolic ratio) was used. For CYP2D6 the MR ratio of dextromethorphan/dextrorphan was used.



Enrollment: 18
Study Start Date: July 2008
Study Completion Date: October 2008
Primary Completion Date: September 2008 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All subjects
Proellex 50 mg CYP1A2 probe CYP2C9 probe CYP2C19 probe CYP2D6 probe CYP3A4 probe
Drug: Proellex
2, 25 mg Proellex capsules administered daily
Other Name: Telapristone acetate
Drug: CYP1A2 probe
Caffeine (200 mg)
Other Name: Caffeine (200 mg)
Drug: CYP2C9 probe
Tolbutamide (250 mg)
Other Name: Tolbutamide (250 mg)
Drug: CYP2C19 probe
Omeprazole (20 mg)
Other Name: Omeprazole (20 mg)
Drug: CYP2D6 probe
Dextromethorphan (30 mg)
Other Name: Dextromethorphan (30 mg)
Drug: CYP3A4 probe
Midazolam (2mg)
Other Name: Midazolam (2mg)

Detailed Description:

This is an open-label, multiple-dose, non-randomized study to assess the drug-drug interactions of Proellex® with cytochrome P450 isoenzymes in healthy female subjects. On Day 1, following an overnight fast and morning void of the bladder, subjects will be administered CYP probe drugs orally. Serial blood samples will be collected at pre-dose and post-dose. Subjects will be administered two Proellex® 25 mg capsules (50 mg total dose) at approximately 0800 hours on Day 2 and 0700 hours on Days 3 through 8. One hour after administration of Proellex® on Day 8, the five CYP probe drugs will be administered and blood and urine samples collected as on Day 1. Blood samples for the determination of plasma concentrations of CDB-4124 and its metabolite CDB-4453 will be collected at pre-dose (trough) on Days 6, 7, and 8 to determine if steady-state conditions have been achieved. Samples will also be collected on Day 8 at 1, 2, 8 and 24 hour after administration of Proellex® to determine the plasma concentrations of CDB-4124 and CDB-4453.

  Eligibility

Ages Eligible for Study:   18 Years to 48 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Healthy adult females
  • A body mass index between 18 and 30 kg/m2, inclusive
  • Negative urine drug and alcohol screen .

Exclusion Criteria:

  • Significant medical condition,
  • Significant physical examination finding
  • Clinical laboratory
  • ECG abnormality
  • CYP2D6 "poor metabolizer"
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00741468

Locations
United States, New Jersey
Clinical Research Center Advanced Biomedical Research Inc.
Hackensack, New Jersey, United States, 07601
Sponsors and Collaborators
Repros Therapeutics Inc.
Investigators
Study Director: Ronald Wiehle, PhD Repros Therapeutics Inc.
  More Information

No publications provided

Responsible Party: Repros Therapeutics Inc.
ClinicalTrials.gov Identifier: NCT00741468     History of Changes
Other Study ID Numbers: ZP-007
Study First Received: August 25, 2008
Results First Received: July 3, 2014
Last Updated: August 20, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Repros Therapeutics Inc.:
Drug-drug interactions
DDI

Additional relevant MeSH terms:
Dextromethorphan
Antitussive Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Respiratory System Agents
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on September 29, 2014