Trial Outcomes & Findings for Safety/Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naive Patients With Cystinosis (NCT NCT01744782)

Last Updated: 2024-12-27

Results Overview

Blood samples were taken 30 minutes after the morning RP103 dose at each study visit to determine White Blood Cell (WBC) cystine concentration. WBC cystine concentrations were determined using liquid chromatography.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

17 participants

Primary outcome timeframe

Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Month 6, Month 9, Month 12, Month 15, Month 18, Study Exit

Results posted on

2024-12-27

Participant Flow

Safety Population: All participants who received at least 1 dose of RP103.

Participant milestones

Participant milestones
Measure	RP103 From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Overall Study STARTED	17
Overall Study COMPLETED	16
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	RP103 From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Overall Study Death	1

Baseline Characteristics

Safety/Effectiveness Study of Cysteamine Bitartrate Delayed-release Capsules (RP103) in Cysteamine Treatment Naive Patients With Cystinosis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	RP103 n=17 Participants From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Age, Continuous	3.80 years STANDARD_DEVIATION 5.116 • n=5 Participants
Sex: Female, Male Female	7 Participants n=5 Participants
Sex: Female, Male Male	10 Participants n=5 Participants

PRIMARY outcome

Timeframe: Day 1, Week 2, Week 4, Week 6, Week 8, Week 10, Week 12, Month 6, Month 9, Month 12, Month 15, Month 18, Study Exit

Population: Participants \<6 years of age who received at least 1 dose of RP103 and who had at least 1 WBC cystine level recorded.

Outcome measures

Outcome measures
Measure	RP103 n=15 Participants From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Day 1	3.1709 nmol 1/2 Cystine/mg protein Standard Deviation 2.95209
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Week 2	2.2899 nmol 1/2 Cystine/mg protein Standard Deviation 3.13707
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Week 4	1.8474 nmol 1/2 Cystine/mg protein Standard Deviation 1.62820
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Week 6	2.3403 nmol 1/2 Cystine/mg protein Standard Deviation 4.31136
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Week 8	0.9589 nmol 1/2 Cystine/mg protein Standard Deviation 1.05851
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Week 10	1.1219 nmol 1/2 Cystine/mg protein Standard Deviation 1.27413
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Week 12	1.1828 nmol 1/2 Cystine/mg protein Standard Deviation 1.31272
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Month 6	2.7250 nmol 1/2 Cystine/mg protein Standard Deviation 1.08187
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Month 9	2.0196 nmol 1/2 Cystine/mg protein Standard Deviation 1.90931
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Month 12	0.8012 nmol 1/2 Cystine/mg protein Standard Deviation 0.59706
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Month 15	1.2443 nmol 1/2 Cystine/mg protein Standard Deviation 1.47616
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Month 18	0.7356 nmol 1/2 Cystine/mg protein Standard Deviation 0.64027
Mean White Blood Cell (WBC) Cystine Concentration at Each Visit Study Exit	0.8197 nmol 1/2 Cystine/mg protein Standard Deviation 0.76413

SECONDARY outcome

Timeframe: Day 1 through study exit

Population: Safety population: All participants who received at least 1 dose of RP103.

Safety was assessed by the incidence of treatment-emergent adverse events (TEAEs) and treatment-emergent serious adverse events (SAEs). An AE/adverse experience was any untoward medical occurrence in a patient or clinical investigation subject administered a pharmaceutical product and which did not necessarily have a causal relationship with this treatment. For additional information regarding adverse events, please see the safety section of the record.

Outcome measures

Outcome measures
Measure	RP103 n=17 Participants From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Number of Participants With Adverse Events	17 Participants

SECONDARY outcome

Timeframe: 30 minutes after the morning RP103 dose at Month 6 (prior to Protocol Amendment 1) or 0 (pre-dose), 30 minutes, 2, 3, 4, 6, 8, 10, and 12 hours after the morning RP103 dose at Month 6 for those enrolled under Protocol Amendment 1 or later

Population: Participants age \<6 years who received at least 1 dose of RP103 and participated in frequent sampling at the Month 6 visit.

Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. The maximum observed plasma concentration (Cmax) of cysteamine was determined directly from the data.

Outcome measures

Outcome measures
Measure	RP103 n=11 Participants From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Maximum Observed Plasma Concentration (Cmax) of Cysteamine	1.26 mg/L Standard Deviation 0.86

SECONDARY outcome

Population: Participants age \<6 years who received at least 1 dose of RP103 and participated in frequent sampling at the Month 6 visit.

Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. The time of the maximum observed plasma concentration (Tmax) of cysteamine was determined directly from the data.

Outcome measures

Outcome measures
Measure	RP103 n=11 Participants From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Time of the Maximum Observed Plasma Concentration (Tmax) of Cysteamine	199 minutes Standard Deviation 138

SECONDARY outcome

Population: Participants age \<6 years who received at least 1 dose of RP103 and participated in frequent sampling at the Month 6 visit.

Blood samples were collected and plasma cysteamine concentration was determined using liquid chromatography. AUC values were estimated using non-compartmental analysis methods. AUClast was defined as the area under the plasma concentration versus time curve, from time 0 to the time of the last measurable concentration (720 minutes). AUCinf was defined as the area under the plasma concentration-versus-time curve from time 0 to infinity.

Outcome measures

Outcome measures
Measure	RP103 n=11 Participants From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Area Under the Plasma Concentration Versus Time Curve (AUC) of Cysteamine AUClast	206 min*mg/L Standard Deviation 113
Area Under the Plasma Concentration Versus Time Curve (AUC) of Cysteamine AUCinf	231 min*mg/L Standard Deviation 123

Adverse Events

RP103

Serious events: 12 serious events

Other events: 16 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	RP103 n=17 participants at risk From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Infections and infestations Gastroenteritis	29.4% 5/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Catheter Site Infection	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Clostridium difficile Colitis	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Gastroenteritis Viral	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Dehydration	23.5% 4/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Electrolyte Imbalance	11.8% 2/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Failure to Thrive	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Hypernatraemia	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Hypocalcaemia	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Malnutrition	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Metabolic Acidosis	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Gastrointestinal disorders Vomiting	23.5% 4/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Gastrointestinal disorders Abdominal Distension	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Surgical and medical procedures Gastrostomy	11.8% 2/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Blood and lymphatic system disorders Anaemia	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Cardiac disorders Cardiopulmonary Failure	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Congenital, familial and genetic disorders Fanconi Syndrome	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Vascular disorders Hypovolaemic Shock	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).

Other adverse events

Other adverse events
Measure	RP103 n=17 participants at risk From Day 1 and throughout the duration of participation, RP103 (Cysteamine Bitartrate Delayed-release Capsules) was administered every 12 hours (Q12H), supplied as 75 mg and 25 mg capsules.
Gastrointestinal disorders Vomiting	70.6% 12/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Gastrointestinal disorders Diarrhoea	35.3% 6/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Gastrointestinal disorders Breath Odour	23.5% 4/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Gastrointestinal disorders Nausea	17.6% 3/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Gastrointestinal disorders Abdominal Pain	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Upper Respiratory Tract Infection	47.1% 8/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Gastroenteritis	17.6% 3/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Rhinitis	17.6% 3/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Catheter Site Infection	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Otitis Media	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Pharyngitis	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Sinusitis	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Infections and infestations Varicella	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
General disorders Pyrexia	23.5% 4/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
General disorders Granuloma	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
General disorders Medical Device Site Reaction	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Respiratory, thoracic and mediastinal disorders Cough	23.5% 4/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Respiratory, thoracic and mediastinal disorders Rhinorrhoea	11.8% 2/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Respiratory, thoracic and mediastinal disorders Epistaxis	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Decreased Appetite	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Hypernatraemia	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Hypokalaemia	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Metabolism and nutrition disorders Malnutrition	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Eye disorders Conjunctivitis	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Eye disorders Strabismus	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Nervous system disorders Headache	11.8% 2/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Skin and subcutaneous tissue disorders Dermatitis Diaper	11.8% 2/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Surgical and medical procedures Gastrostomy Closure	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Surgical and medical procedures Gastrostomy Tube Removal	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Blood and lymphatic system disorders Anaemia	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Musculoskeletal and connective tissue disorders Foot Deformity	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Reproductive system and breast disorders Perineal Erythema	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).
Vascular disorders Hypertension	5.9% 1/17 • From Day 1 through study exit Adverse events (AEs) were defined as any AE with onset following initial drug administration (on Day 1).

Additional Information

Evelyn Olson, Director

Horizon Pharma USA, Inc.

Phone: 224-383-3000

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Horizon requests that any Investigator/institution that plans on presenting or publishing results provide written notification of their request a minimum of 60 days prior to presentation or publication. The Sponsor may request that Confidential Information be deleted and/or the publication be postponed in order to protect the Sponsors' Intellectual Property rights .
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