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

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:

MedlinePlus related topics: Caffeine Drug Reactions

Drug Information available for: Tolbutamide Dextromethorphan hydrobromide Dextromethorphan Omeprazole

U.S. FDA Resources

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)

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 (Adult)
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


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:


Midazolam Caffeine Dextromethorphan Omeprazole Tolbutamide Adjuvants, Anesthesia Hypnotics and Sedatives Central Nervous System Depressants Physiological Effects of Drugs Anti-Anxiety Agents Tranquilizing Agents Psychotropic Drugs Anesthetics, Intravenous Anesthetics, General Anesthetics	GABA Modulators GABA Agents Neurotransmitter Agents Molecular Mechanisms of Pharmacological Action Central Nervous System Stimulants Phosphodiesterase Inhibitors Enzyme Inhibitors Purinergic P1 Receptor Antagonists Purinergic Antagonists Purinergic Agents Anti-Ulcer Agents Gastrointestinal Agents Proton Pump Inhibitors Antitussive Agents Respiratory System Agents

ClinicalTrials.gov processed this record on September 29, 2016