A Single Dose Evaluation of the Effects of Renal Impairment on Deflazacort Pharmacokinetics

• Status: Completed
• Trial end date: 2015-02-01
• Target enrollment: 0
• Participant gender: All

Summary

This is a non-randomized, open-label, single-dose study to compare the PK of 21 desacetyl-DFZ and, if data permits, deflazacort in 8 subjects with ESRD to that of 8 healthy matched control subjects (age, body mass index [BMI], and gender).

• Phase: Phase 1
• Accepts Healthy Volunteers?: Accepts Healthy Volunteers

Details

• Lead Sponsor: Marathon Pharmaceuticals, LLC; PTC Therapeutics
• Treatments: Deflazacort

Criteria

Inclusion Criteria:

• Continuous non-smokers or moderate smokers

• 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 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 dosing until 90 days Subject with ESRD on Hemodialysis

• Adult male or female, 18 80 years of age

• BMI ≥ 18.5 and ≤ 40.0 kg/m2 - Subject is maintained on a stable regimen of HD at least 3 months Healthy Subject

• Healthy adult male and female subjects will be matched 1:1 to a specific subject in the ESRD cohort based upon age, BMI, and gender [1:1]. The following criteria should be fulfilled:

• 18 to 80 years of age. Age must be within ± 15 years of the matched subject's age in the ESRD cohort

• BMI ≥ 18.5 and ≤ 40.0 kg/m2. BMI must be within ± 15% of the matched subject's BMI in the ESRD cohort

• Has a CLcr ≥ 90 mL/min

Exclusion Criteria:

• 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 hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (e.g., steroids or their formulations including lactose and corn starh)

• History (within the last year prior to dosing) or presence of peptic ulcers

• History or presence of:

• Gastritis or esophagitis, diverticulitis, ulcerative colitis (if there is probability of impending perforation), abscess or pyogenic infections, or fresh intestinal anastomosis

• Previous corticoids-induced myopathy

• Ocular herpes simplex

• 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

• Osteoporosis

• Myasthenia gravis

• Epilepsy

• Idiopathic hypocalcuria

• Seated blood pressure is less than 90/40 mmHg or greater than 170/100 mmHg

• Seated heart rate is lower than 40 bpm or higher than 99 bpm

• QTcF interval is > 500 msec

• Has received any live or live-attenuated vaccine within 30 days

• Has received any immunosuppressive agents, coal tar, and/or radiation therapies within 30 days

• Has received injectable corticoids in the 12 weeks prior to dosing or any oral form of corticoids in 30 days

• Unable to refrain from or anticipates the use of:

• Any drug known to be moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A or P-glycoprotein (P-gp) for 14 days or 28 days, respectively

• Any medication or substance which cannot be discontinued at least 14 days

• Female subjects of childbearing potential

• Female subjects who are pregnant or lactating

• Positive results at screening for HIV, HBsAg or HCV

• Has been on a diet incompatible with the on study diet within 28 days

• Donation of blood or significant blood loss within 56 days

• Plasma donation within 7 days

• Participation in another clinical trial within 28 days Subject with ESRD

• Is a regular user of any medication that would significantly alter glomerular filtration rate, e.g., cimetidine

• Has presence of a renal carcinoma or acute renal disease caused by infection or drug toxicity

• History of drug abuse within the past 2 years

• Has a positive urine/breath alcohol or urine/serum/saliva drug testing Normal Renal Function

• History or presence of alcoholism or drug abuse within the past 2 years

• Positive urine drug or urine/breath alcohol results