Evaluate Effects of Multiple Doses of Rifampin and Clarithromycin on the Single Dose Pharmacokinetics of Deflazacort

NCT02286635 | Completed Phase 1

• 1 other identifier: MP-104-CL-025
• Study Type: interventional
• Target: 58
• Locations: 1 country
• Sites: 1

Brief Summary

The primary objective of the study is to determine the potential effects of multiple doses of rifampin and clarithromycin on the single dose pharmacokinetics (PK) of the deflazacort active metabolite (21 desacetyl-DFZ) in healthy adult subjects.

Conditions

Healthy Volunteers

Outcome Measures

Primary Outcomes (1)

• Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.

  Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.

  10 days and 4 days

Secondary Outcomes (1)

• Safety and tolerability of one dose of deflazacort in healthy subjects receiving CYP3A4 inhibitors and inducers as measured by capturing occurrence of adverse events.

  10 days and 4 days

Study Arms (2)

Cohort A Deflazacort and Rifampin

EXPERIMENTAL

Subjects will recieve one 18 mg dose of deflazacort on Day 1, Period 1 and Day 10, Period 2; cohort A. Subjects will receive once daily dosing of rifampin on Day 1, Period 2 through Day 10, Period 2.

Drug: Deflazacort and rifampin

Cohort B Deflazacort and Clarithromycin

EXPERIMENTAL

Subjects will recieve one 18 mg dose of deflazacort on Day 1, Period 1 and Day 4, period 2; cohort B. Subjects will receive twice daily dosing of clarithromycin on Day 1, Period 2 through Day 4, Period 2.

Drug: Deflazacort and Clarithromycin

Interventions

Deflazacort and rifampin DRUG

Deflazacort, a glucocorticoid with anti-inflammatory and immunosuppressive effects, is used in treating a variety of diseases. Pharmacologically it is an inactive pro-drug which is metabolized completely and rapidly to the active drug 21-desacetyldeflazacort (21 desacetyl-DFZ). The elimination of this metabolite is primarily via the urine in humans. Its potency is approximately 70 to 90% of prednisone and 6 mg of deflazacort has approximately the same anti-inflammatory potency as 5 mg of prednisolone or prednisone. Rifampin is a potent inducer of drug metabolism by inducing a variety of hepatic and intestinal CYP enzymes, especially CYP3A4. Rifampin is a semi-synthetic antibiotic.

Also known as: DFZ

Cohort A Deflazacort and Rifampin

Deflazacort and Clarithromycin DRUG

Deflazacort, a glucocorticoid with anti-inflammatory and immunosuppressive effects. It is an inactive pro-drug which is metabolized completely and rapidly to the active drug 21 desacetyl-DFZ. The elimination of this metabolite is primarily via the urine in humans. Its potency is approximately 70 to 90% of prednisone. Clarithromycin is a semi-synthetic macrolide antibiotic. Clarithromycin is active in vitro against a variety of aerobic and anaerobic gram-positive and gram-negative bacteria as well as most mycobacterium avium complex (MAC) bacteria. Additionally, the 14-OH clarithromycin metabolite also has clinically significant antimicrobial activity. Clarithromycin is indicated for the treatment of mild to moderate infections such as pharyngitis/tonsillitis.

Also known as: biaxin

Cohort B Deflazacort and Clarithromycin

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy, adult, male or female, 18 55 years of age
• Continuous non smoker who has not used nicotine containing products for at least 3 months
• Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2
• For a female of non childbearing potential: must have undergone a sterilization procedures or be postmenopausal with amenorrhea for at least 1 year prior to the first dose of study drug and FSH serum levels consistent with postmenopausal status
• A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days
• If male, must agree not to donate sperm from the first dose of study drug until 90 days

You may not qualify if:

• Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
• History or presence of alcoholism or drug abuse within the past 2 years
• History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (e.g., steroids or their formulations including lactose)
• History or presence of:
• Symptomatic cardiomyopathy at screening
• Immunosuppression or other contraindications for corticosteroid treatment
• History of chronic systemic fungal or viral infections
• Galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption
• Diabetes mellitus
• Osteoporosis
• Myasthenia gravis
• Epilepsy
• Idiopathic hypocalcuria
• Hypothyroidism (TSH clinically significant)
• Gastrointestinal issues or ulcers

Sponsors & Collaborators

• PTC Therapeutics: lead

Study Sites (1)

Celerion

Tempe, Arizona, 85283, United States

Location

MeSH Terms

Interventions

deflazacort; Rifampin; Clarithromycin

Intervention Hierarchy (Ancestors)

Rifamycins; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Lactams, Macrocyclic; Macrocyclic Compounds; Polycyclic Compounds; Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Officials

• Bioscience Center

  Marathon Pharmaceuticals, LLC

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2014
• First Posted: November 10, 2014
• Study Start: November 1, 2014
• Primary Completion: December 1, 2014
• Study Completion: December 1, 2014
• Last Updated: August 18, 2017

Record last verified: 2017-08

Locations

US (1)