Trial Outcomes & Findings for Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of RP103 Compared to Cystagon® in Patients With Cystinosis (NCT NCT00872729)
NCT ID: NCT00872729
Last Updated: 2024-12-19
Results Overview
Recruitment status
COMPLETED
Study phase
PHASE1/PHASE2
Target enrollment
9 participants
Primary outcome timeframe
12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosing
Results posted on
2024-12-19
Participant Flow
Participant milestones
| Measure |
Cystagon® and RP103
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules,150 mg/50 mg; Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules,75 mg; Single-dose, open-label, nonrandomized, 2-period, crossover study of cysteamine bitartrate delayed-release capsules (RP103) and Cystagon®. Subjects were enrolled sequentially and received Cystagon® first followed by RP103.
|
|---|---|
|
Overall Study
STARTED
|
9
|
|
Overall Study
COMPLETED
|
9
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Pilot Study of Safety, Tolerability, Pharmacokinetics/Pharmacodynamics of RP103 Compared to Cystagon® in Patients With Cystinosis
Baseline characteristics by cohort
| Measure |
Cystagon® and RP103
n=9 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules,150 mg/50 mg; Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules,75 mg.
|
|---|---|
|
Age, Categorical
<=18 years
|
8 Participants
n=5 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
1 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=5 Participants
|
|
Age, Continuous
|
12.8 years
STANDARD_DEVIATION 4.76 • n=5 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
9 participants
n=5 Participants
|
PRIMARY outcome
Timeframe: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosingOutcome measures
| Measure |
Cystagon®
n=9 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103
n=9 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (1 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (1 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (2 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (2 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (2.5 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (2.5 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (3 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (3 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (4 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (4 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (6 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (6 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (8 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (8 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (10 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (10 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (12 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (12 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetic Parameter: Cmax of Cysteamine
|
42.02 umol/L
Geometric Coefficient of Variation 51
|
33.06 umol/L
Geometric Coefficient of Variation 55
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 12 hours post RP103 dosing and 7 hours post 1st Cystagon® dosingOutcome measures
| Measure |
Cystagon®
n=9 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103
n=9 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (1 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (1 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (2 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (2 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (2.5 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (2.5 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (3 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (3 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (4 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (4 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (6 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (6 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (8 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (8 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (10 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (10 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (12 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (12 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetic Parameter: Tmax of Cysteamine
|
1.00 hour
Interval 0.5 to 2.0
|
3.00 hour
Interval 0.0 to 5.13
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: 12 hours post RP103 dosing and 6 hours post 1st Cystagon® dosingPopulation: Subjects were enrolled sequentially according to the study design. A mixed-effects linear model was used to assess differences between the RP103 and Cystagon treatment groups. Sample size is based on feasibility rather than statistical considerations.
t = 6 for Cystagon and t = 12 for RP103. Cystagon is dosed every 6 hours and there is no measurement after 6 hours and up to 12 hours.
Outcome measures
| Measure |
Cystagon®
n=9 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103
n=9 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (1 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (1 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (2 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (2 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (2.5 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (2.5 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (3 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (3 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (4 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (4 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (6 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (6 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (8 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (8 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (10 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (10 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (12 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (12 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Plasma Pharmacokinetic Parameter: AUC(0-t) of Cysteamine
|
107.89 umol•h/L
Geometric Coefficient of Variation 58
|
119.17 umol•h/L
Geometric Coefficient of Variation 46
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
—
|
PRIMARY outcome
Timeframe: up to 12 hours post Cystagon® dosing and RP103 dosingPopulation: Sample size is based on feasibility rather than statistical considerations. Analysis time differences (0-6 hours) is due to different absorption characteristics of Cysteamine between RP103 and Cystagon. Cystagon is dosed every 6 hours and there is no measurement after 6 hours and up to 12 hours.
The pharmacodynamic (PD) parameter measures the changes of WBC cystine level from the baseline. Cystine is a disulfide amino acid formed through oxidation of two molecules of cysteine; hence, cystine's concentration is commonly given in half-cystine equivalents to avoid confusion. The level of cystine in WBC/leukocytes is expressed in units of nmol half-cystine/mg protein (nmol ½ cystine/mg protein). Half-cystine is quantified by a reduction of cystine followed by an assay for cysteine, which is then normalized by the total cellular protein content within the sample using methods of such as Lowry assay, bicinchoninic acid assay, or Bradford.
Outcome measures
| Measure |
Cystagon®
n=6 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (1 Hour)
n=3 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (1 Hour)
n=3 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (2 Hour)
n=6 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (2 Hour)
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (2.5 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (2.5 Hour)
n=6 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (3 Hour)
n=3 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (3 Hour)
n=3 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (4 Hour)
n=6 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (4 Hour)
n=6 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (6 Hour)
n=9 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (6 Hour)
n=6 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (8 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (8 Hour)
n=3 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (10 Hour)
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (10 Hour)
n=3 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
Cystagon® (12 Hour)
n=3 Participants
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg.
|
RP103 (12 Hour)
n=6 Participants
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg.
|
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
|
Pharmacodynamic Parameter: Changes of White Blood Cell (WBC) Cystine Level From Baseline
|
0.11 nmol 1/2 cystine/mg protein
Standard Deviation 0.24
|
—
|
-0.10 nmol 1/2 cystine/mg protein
Standard Deviation 0.02
|
0.87 nmol 1/2 cystine/mg protein
Standard Deviation 0.33
|
-0.07 nmol 1/2 cystine/mg protein
Standard Deviation 0.28
|
—
|
—
|
0.19 nmol 1/2 cystine/mg protein
Standard Deviation 0.48
|
-0.14 nmol 1/2 cystine/mg protein
Standard Deviation 0.06
|
0.43 nmol 1/2 cystine/mg protein
Standard Deviation 0.70
|
-0.01 nmol 1/2 cystine/mg protein
Standard Deviation 0.15
|
0.10 nmol 1/2 cystine/mg protein
Standard Deviation 0.50
|
0.30 nmol 1/2 cystine/mg protein
Standard Deviation 0.34
|
0.22 nmol 1/2 cystine/mg protein
Standard Deviation 0.41
|
—
|
0.20 nmol 1/2 cystine/mg protein
Standard Deviation 0.31
|
—
|
0.45 nmol 1/2 cystine/mg protein
Standard Deviation 0.36
|
0.37 nmol 1/2 cystine/mg protein
Standard Deviation 0.18
|
0.72 nmol 1/2 cystine/mg protein
Standard Deviation 0.47
|
Adverse Events
Cystagon®
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
RP103
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Cystagon®
n=9 participants at risk
Reference Product: Cystagon® (Cysteamine Bitartrate) Capsules, 150 mg/50 mg;
|
RP103
n=9 participants at risk
Test Product: RP103 (Cysteamine Bitartrate) Delayed-release Capsules, 75 mg
|
|---|---|---|
|
Gastrointestinal disorders
Vomiting
|
44.4%
4/9 • Number of events 4 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Gastrointestinal disorders
Nausea
|
33.3%
3/9 • Number of events 3 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Gastrointestinal disorders
Abdominal pain
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Gastrointestinal disorders
Breath odor
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Gastrointestinal disorders
Constipation
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Gastrointestinal disorders
Diarrhoea
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
General disorders
Thirst
|
33.3%
3/9 • Number of events 4 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
22.2%
2/9 • Number of events 2 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Injury, poisoning and procedural complications
Contusion
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Metabolism and nutrition disorders
Anorexia
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Metabolism and nutrition disorders
Hypokalaemia
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Skin and subcutaneous tissue disorders
Skin odour abnormal
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
|
Vascular disorders
Pallor
|
11.1%
1/9 • Number of events 1 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
0.00%
0/9 • After a dose of study drug (RP103 or Cystagon®) on or after study entry, for up to 10 days.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee Investigators may publish or disclose study data, with the restriction that sponsor may embargo such communications for a period up to 60 days from the time submitted to sponsor.
- Publication restrictions are in place
Restriction type: OTHER