Study in Healthy Adults to Determine the Effect That Food Has on the Absorption and Delivery of the Drug Cystagon™

Food-Effect on Bioavailability of Cystagon™ in Normal, Healthy Adults

In order to meet FDA standards of safety and efficacy reporting for most new drugs, food-effect bioavailability (the impact that the presence of food in the digestive tract has on the rate and extent at which a drug is absorbed into the bloodstream and delivered to the site of action) must be collected. Cystagon™ is an FDA approved drug for the treatment of the rare disease cystinosis that became available in 1994, but there is inadequate knowledge of the food-effect on this drug's bioavailability. This study aims to investigate how food affects the absorption of Cystagon™ into the bloodstream of normal healthy adults.

Study Overview

• Status: Completed
• Conditions: Cystinosis; Nephropathic Cystinosis
• Intervention / Treatment: Drug: Cysteamine bitartrate

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • La Jolla, California, United States, 92093
      • University of California, San Diego Center for Clinical Research Services (CCR)

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male or female, smoker (no more than 25 cigarettes daily) or non-smoker, 18 years of age and older, with BMI > 18 and < 30.0.
2. Females of childbearing potential who are sexually active must be willing to use two forms of contraceptive methods throughout the study and for 14days after the last study drug administration.
3. Minimum weight of 50 kg.
4. Good health, defined as not having history of any chronic illness and not requiring any regular medication/therapy.
5. Must swallow tablets on a regular basis.

Exclusion Criteria:

1. Evidence of Helicobacter pylori infection, presently, or within the last year.
2. Subjects with known hypersensitivity to cysteamine.

3. History, currently or within the past 3 months, of the following conditions:

   • Pancreatitis
   • Inflammatory bowel disease
   • Malabsorption
   • Severe liver disease
   • Unstable heart disease, e.g., myocardial infarction, heart failure, arrhythmias.
   • Unstable diabetes mellitus
   • Any bleeding disorder.
   • Zollinger-Ellison syndrome
   • Malignant disease
4. Subjects whom may be pregnant or have health issues that make it unsafe for them participate, or whose concomitant medical problems preclude them from committing to the study schedule.
5. Use of an investigational drug within 30 days (or 90 days for biologics) prior to dosing.
6. Use of prescription medication within 14 days prior to the first dosing;
7. Use over-the-counter products including natural health products (e.g. food supplements and herbal supplements) within 7 days prior to the first dosing.
8. Donation of plasma within 7 days prior to dosing. Donation or loss of blood (excluding volume drawn at screening) of 50 mL to 499 mL of blood within 30 days, or more than 499 mL within 56 days prior to dosing.
9. Hemoglobin <13.5 g/dL (males) and <12.0 g/dL (females) and hematocrit <41.0% (males) and <36.0% (females) at screening.
10. Breast-feeding subject.
11. Immunization with a live attenuated vaccine 1 month prior to dosing or planned vaccination during the course of the study.

12. Presence of fever (body temperature >37.6°C) (e.g. a fever associated with a symptomatic viral or bacterial infection) within 2 weeks prior to dosing.

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Study Plan

How is the study designed?

Design Details

• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Cysteamine bitartrate; Cysteamine bitartrate, 500mg once a day, three days.	Drug: Cysteamine bitartrate; 500 mg total, single dose taken orally on visits 2, 3 & 4 which must occur within a 14 day period.; Other Names: Cystagon; Cysteamine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cysteamine Absorption: Area Under the Plasma Concentration Curve (AUC)	Subjects were randomized to one of two possible treatment sequences using block randomization: Sequence 1 - fasted, high-fat, high-protein or Sequence 2 - high-protein, high-fat, fasted. Sequence assignment determined the treatment condition corresponding to Period I, II & III visits.	0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180 minutes, and 3.5, 4, 4.5, 5, 6 hours post-dose
Peak Plasma Cysteamine Concentration (Cmax)	Subjects were randomized to one of two possible treatment sequences using block randomization: Sequence 1 - fasted, high-fat, high-protein or Sequence 2 - high-protein, high-fat, fasted. Sequence assignment determined the treatment condition corresponding to Period I, II & III visits.	0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180 minutes, and 3.5, 4, 4.5, 5, 6 hours post-dose
Time to Peak Plasma Cysteamine Concentration (Tmax)	Subjects were randomized to one of two possible treatment sequences using block randomization: Sequence 1 - fasted, high-fat, high-protein or Sequence 2 - high-protein, high-fat, fasted. Sequence assignment determined the treatment condition corresponding to Period I, II & III visits.	0, 15, 30, 45, 60, 75, 90, 105, 120, 135, 150, 165, 180 minutes, and 3.5, 4, 4.5, 5, 6 hours post-dose

Collaborators and Investigators

• Sponsor: University of California, San Diego
• Collaborators: Raptor Pharmaceuticals Corp.
• Investigators: Principal Investigator: Ranjan Dohil, M.D., University of California, San Diego

Publications and helpful links

General Publications

• Gahl WA, Thoene JG, Schneider JA. Cystinosis. N Engl J Med. 2002 Jul 11;347(2):111-21. doi: 10.1056/NEJMra020552. No abstract available.
• Gahl WA, Reed GF, Thoene JG, Schulman JD, Rizzo WB, Jonas AJ, Denman DW, Schlesselman JJ, Corden BJ, Schneider JA. Cysteamine therapy for children with nephropathic cystinosis. N Engl J Med. 1987 Apr 16;316(16):971-7. doi: 10.1056/NEJM198704163161602.
• Markello TC, Bernardini IM, Gahl WA. Improved renal function in children with cystinosis treated with cysteamine. N Engl J Med. 1993 Apr 22;328(16):1157-62. doi: 10.1056/NEJM199304223281604.
• Smolin LA, Clark KF, Thoene JG, Gahl WA, Schneider JA. A comparison of the effectiveness of cysteamine and phosphocysteamine in elevating plasma cysteamine concentration and decreasing leukocyte free cystine in nephropathic cystinosis. Pediatr Res. 1988 Jun;23(6):616-20. doi: 10.1203/00006450-198806000-00018.

Study record dates

Study Major Dates

• Study Start: September 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: September 9, 2011
• First Submitted That Met QC Criteria: September 12, 2011
• First Posted (ESTIMATE): September 13, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): October 9, 2013
• Last Update Submitted That Met QC Criteria: September 23, 2013
• Last Verified: September 1, 2013

More Information

Terms related to this study

• Keywords: Metabolic Diseases; Metabolism, Inborn Errors; Lysosomal Storage Diseases
• Additional Relevant MeSH Terms: Metabolic Diseases; Kidney Diseases; Urologic Diseases; Genetic Diseases, Inborn; Metabolism, Inborn Errors; Lysosomal Storage Diseases; Renal Tubular Transport, Inborn Errors; Fanconi Syndrome; Cystinosis; Molecular Mechanisms of Pharmacological Action; Cystine Depleting Agents; Cysteamine
• Other Study ID Numbers: 111011