Cystinosis, Nephropathic Cystinosis
Conditions
Keywords
Lysosomal Storage Diseases, Metabolic Diseases, Metabolism, Inborn Errors
Brief summary
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.
Interventions
500 mg total, single dose taken orally on visits 2, 3 & 4 which must occur within a 14 day period.
Sponsors
Raptor Pharmaceuticals Corp.
University of California, San Diego
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
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. \-
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cysteamine Absorption: Area Under the Plasma Concentration Curve (AUC) | 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 | 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. |
| Peak Plasma Cysteamine Concentration (Cmax) | 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 | 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. |
| Time to Peak Plasma Cysteamine Concentration (Tmax) | 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 | 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. |
Countries
United States
Participant flow
Recruitment details
Recruitment period: 09/19/2011 - 11/21/2012 Recruitment Locations: medical centers
Pre-assignment details
Screening for liver function and H pylori infection and brief medical history in order to determine if all inclusion and exclusion criteria were met. One enrollee met all inclusion criteria but clinical lab test revealed presence of H Pylori, an exclusion factor. Two enrollees withdrew from the trial prior to assignment due to scheduling conflicts.
Participants by arm
| Arm | Count |
|---|---|
| Cysteamine Bitartrate Cysteamine bitartrate, 500mg once a day, three days.
Cysteamine bitartrate : 500 mg total, single dose taken orally on visits 2, 3 & 4 which must occur within a 14 day period. | 8 |
| Total | 8 |
Baseline characteristics
| Characteristic | Cysteamine Bitartrate |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 8 Participants |
| Age Continuous | 29.9 years STANDARD_DEVIATION 8.5 |
| Region of Enrollment United States | 8 participants |
| Sex: Female, Male Female | 3 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 3 / 8 |
| serious Total, serious adverse events | 0 / 8 |
Outcome results
Primary
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cysteamine Bitartrate | Cysteamine Absorption: Area Under the Plasma Concentration Curve (AUC) | Fasted | 3618 min*uM | Standard Deviation 372 |
| Cysteamine Bitartrate | Cysteamine Absorption: Area Under the Plasma Concentration Curve (AUC) | Fed High-Fat/Calorie | 2799 min*uM | Standard Deviation 405 |
| Cysteamine Bitartrate | Cysteamine Absorption: Area Under the Plasma Concentration Curve (AUC) | Fed High-Protein | 2457 min*uM | Standard Deviation 353 |
Comparison: High-fat/calorie compared to fasted conditionp-value: 0.04ANOVA
Comparison: High-protein compared to fasted conditionp-value: 0.005ANOVA
Primary
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cysteamine Bitartrate | Peak Plasma Cysteamine Concentration (Cmax) | Fed High-Protein | 17.2 uM | Standard Deviation 2.6 |
| Cysteamine Bitartrate | Peak Plasma Cysteamine Concentration (Cmax) | Fasted | 26.3 uM | Standard Deviation 3.5 |
| Cysteamine Bitartrate | Peak Plasma Cysteamine Concentration (Cmax) | Fed High-Fat/Calorie | 22.4 uM | Standard Deviation 5.6 |
Comparison: High-fat/calorie compared to fasted conditionp-value: 0.16ANOVA
Comparison: High-protein compared to fasted conditionp-value: 0.036ANOVA
Primary
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.
Time frame: 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
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cysteamine Bitartrate | Time to Peak Plasma Cysteamine Concentration (Tmax) | Fasted | 71.2 minutes | Standard Deviation 12.9 |
| Cysteamine Bitartrate | Time to Peak Plasma Cysteamine Concentration (Tmax) | Fed High-Fat/Calorie | 106.9 minutes | Standard Deviation 28.8 |
| Cysteamine Bitartrate | Time to Peak Plasma Cysteamine Concentration (Tmax) | Fed High-Protein | 120 minutes | Standard Deviation 23.4 |
Comparison: Fed high-fat/calorie compared to fasted condition.p-value: 0.3Non-parametric Hodges-Lehmann method
Comparison: High-protein compared to fasted conditionp-value: 0.05Non-parametric Hodges-Lehmann method