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Trial record 5 of 32 for:    CYSTEAMINE

Long-Term Safety Follow-up Study of Cysteamine Bitartrate Delayed-release Capsules (RP103)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01197378
Recruitment Status : Completed
First Posted : September 9, 2010
Results First Posted : July 24, 2018
Last Update Posted : July 24, 2018
Sponsor:
Information provided by (Responsible Party):
Horizon Pharma USA, Inc.

Study Type Interventional
Study Design Intervention Model: Single Group Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Condition Cystinosis
Intervention Drug: Cysteamine Bitartrate Delayed-release Capsules
Enrollment 60
Recruitment Details Initially, only patients who completed the previous Phase III Study RP103-03 (NCT01000961) were enrolled in this extension study. As of 27 September 2011, enrollment was opened up to additional participants, including children who were less than 6 years of age and kidney transplant subjects who qualified based on the inclusion/exclusion criteria.
Pre-assignment Details  
Arm/Group Title Cysteamine Bitartrate
Hide Arm/Group Description Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months.
Period Title: Overall Study
Started 60
Received Treatment 59
Completed 53
Not Completed 7
Reason Not Completed
Adverse Event             3
Withdrawal by Subject             1
Physician Decision             1
Other             2
Arm/Group Title Cysteamine Bitartrate
Hide Arm/Group Description Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months.
Overall Number of Baseline Participants 59
Hide Baseline Analysis Population Description
Safety population
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 59 participants
10.9  (6.00)
Age, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
≤ 6 years
13
  22.0%
> 6 to ≤ 12 years
25
  42.4%
> 12 to ≤ 21 years
19
  32.2%
> 21 years
2
   3.4%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
Female
22
  37.3%
Male
37
  62.7%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
Hispanic or Latino
3
   5.1%
Not Hispanic or Latino
56
  94.9%
Unknown or Not Reported
0
   0.0%
Race/Ethnicity, Customized  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 59 participants
White
58
  98.3%
Other
1
   1.7%
1.Primary Outcome
Title Number of Participants With Treatment-emergent Adverse Events
Hide Description

Drug-related adverse events (AEs) are AEs the investigator assessed as having relation to drug of 'possibly', 'probably' or 'definitely'.

The severity of AEs was categorized according to the Common Terminology Criteria for Adverse Events (CTCAE), Version 3.0 as follows:

  • Mild (Grade 1): experience is minor and does not cause significant discomfort to subject or change in activities of daily living (ADL); subject is aware of symptoms but symptoms are easily tolerated;
  • Moderate (Grade 2): experience is an inconvenience or concern to the subject and causes interference with ADL, but the subject is able to continue with ADL.
  • Severe (Grade 3): experience significantly interferes with ADL and the subject is incapacitated and/or unable to continue with ADL
  • Life-threatening (Grade 4): experience that, in the view of the Investigator, places the subject at immediate risk of death from the event as it occurred.
Time Frame From first dose of study drug to 7 days after the last dose; median duration of treatment was 1461 days.
Hide Outcome Measure Data
Hide Analysis Population Description
All participants who received at least 1 dose of cysteamine bitartrate.
Arm/Group Title Cysteamine Bitartrate
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months.
Overall Number of Participants Analyzed 59
Measure Type: Count of Participants
Unit of Measure: Participants
Any adverse event
58
  98.3%
Adverse events related to study drug
37
  62.7%
Adverse events ≥ Grade 3
24
  40.7%
Serious adverse events
32
  54.2%
Adverse events leading to discontinuation
3
   5.1%
2.Secondary Outcome
Title Trough Plasma Cysteamine Concentration
Hide Description Plasma cysteamine concentration was determined using methods employing Hydrophilic Interaction Liquid Chromatography (HILC) high pressure liquid chromatography (HPLC) tandem mass spectrometry (HPLC-MS/MS).
Time Frame Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic/Pharmacodynamic (PK/PD) Population includes all participants who had at least one PK/PD measurement. Day 1 results only include participants who did not complete Study RP103-03.
Arm/Group Title Cysteamine Bitartrate
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: mg/L
Day 1 Number Analyzed 19 participants
0.17  (0.093)
Month 6 Number Analyzed 56 participants
0.29  (0.613)
Year 1 Number Analyzed 56 participants
0.37  (0.513)
Year 1.5 Number Analyzed 55 participants
0.48  (0.718)
Year 2 Number Analyzed 45 participants
0.36  (0.412)
Year 3 Number Analyzed 28 participants
0.34  (0.659)
Year 4 Number Analyzed 38 participants
0.47  (0.708)
Year 5 Number Analyzed 26 participants
0.40  (0.399)
3.Secondary Outcome
Title White Blood Cell Cystine Concentration
Hide Description White blood cell (WBC) cystine concentration was determined using high performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS).
Time Frame Day 1 (predose) and Month 6, Years 1, 1.5, 2, 3, 4 and 5 at 0.5 hours post-dose
Hide Outcome Measure Data
Hide Analysis Population Description
The Pharmacokinetic/Pharmacodynamic (PK/PD) Population includes all participants who had at least one PK/PD measurement. Day 1 results only include participants who did not complete Study RP103-03.
Arm/Group Title Cysteamine Bitartrate
Hide Arm/Group Description:
Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months.
Overall Number of Participants Analyzed 59
Mean (Standard Deviation)
Unit of Measure: nmol 1/2 Cystine/mg protein
Day 1 Number Analyzed 18 participants
1.68  (1.275)
Month 6 Number Analyzed 56 participants
0.93  (1.174)
Year 1 Number Analyzed 55 participants
0.65  (0.569)
Year 1.5 Number Analyzed 54 participants
0.75  (0.852)
Year 2 Number Analyzed 44 participants
0.65  (0.851)
Year 3 Number Analyzed 28 participants
0.66  (0.575)
Year 4 Number Analyzed 28 participants
1.38  (1.672)
Year 5 Number Analyzed 24 participants
1.17  (2.117)
Time Frame From first dose of study drug to 7 days after last dose; median duration of treatment was 1461 days.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cysteamine Bitartrate
Hide Arm/Group Description Cysteamine bitartrate delayed-release capsules were administered twice daily for up to 96 months.
All-Cause Mortality
Cysteamine Bitartrate
Affected / at Risk (%)
Total   0/59 (0.00%) 
Show Serious Adverse Events Hide Serious Adverse Events
Cysteamine Bitartrate
Affected / at Risk (%)
Total   32/59 (54.24%) 
Blood and lymphatic system disorders   
Anaemia  1  2/59 (3.39%) 
Cardiac disorders   
Congestive cardiomyopathy  1  1/59 (1.69%) 
Congenital, familial and genetic disorders   
Arnold-chiari malformation  1  1/59 (1.69%) 
Cryptorchism  1  1/59 (1.69%) 
Gastrointestinal disorders   
Vomiting  1  4/59 (6.78%) 
Diarrhoea  1  2/59 (3.39%) 
Constipation  1  1/59 (1.69%) 
Gastric fistula  1  1/59 (1.69%) 
Gastrooesophageal reflux disease  1  1/59 (1.69%) 
Peritonitis  1  1/59 (1.69%) 
General disorders   
Impaired healing  1  1/59 (1.69%) 
Immune system disorders   
Kidney transplant rejection  1  1/59 (1.69%) 
Infections and infestations   
Appendicitis  1  7/59 (11.86%) 
Gastroenteritis  1  6/59 (10.17%) 
Appendicitis perforated  1  1/59 (1.69%) 
Bacterial diarrhoea  1  1/59 (1.69%) 
Otitis media chronic  1  1/59 (1.69%) 
Pneumonia  1  1/59 (1.69%) 
Pyelonephritis  1  1/59 (1.69%) 
Respiratory tract infection viral  1  1/59 (1.69%) 
Salpingitis  1  1/59 (1.69%) 
Tooth abscess  1  1/59 (1.69%) 
Urethritis  1  1/59 (1.69%) 
Injury, poisoning and procedural complications   
Alcohol poisoning  1  1/59 (1.69%) 
Fracture  1  1/59 (1.69%) 
Graft dysfunction  1  1/59 (1.69%) 
Investigations   
Biopsy kidney  1  2/59 (3.39%) 
Investigation  1  1/59 (1.69%) 
Metabolism and nutrition disorders   
Dehydration  1  5/59 (8.47%) 
Hypokalaemia  1  4/59 (6.78%) 
Acidosis  1  1/59 (1.69%) 
Electrolyte imbalance  1  1/59 (1.69%) 
Hypocalcaemia  1  1/59 (1.69%) 
Hyponatraemia  1  1/59 (1.69%) 
Malnutrition  1  1/59 (1.69%) 
Musculoskeletal and connective tissue disorders   
Knee deformity  1  5/59 (8.47%) 
Nervous system disorders   
Convulsion  1  1/59 (1.69%) 
Epilepsy  1  1/59 (1.69%) 
Loss of consciousness  1  1/59 (1.69%) 
Pseudoparalysis  1  1/59 (1.69%) 
Pregnancy, puerperium and perinatal conditions   
Abortion spontaneous  1  1/59 (1.69%) 
Psychiatric disorders   
Abnormal behavior  1  1/59 (1.69%) 
Impaired self-care  1  1/59 (1.69%) 
Mental disorder  1  1/59 (1.69%) 
Renal and urinary disorders   
Renal failure chronic  1  4/59 (6.78%) 
Renal failure  1  3/59 (5.08%) 
Renal failure acute  1  1/59 (1.69%) 
Renal impairment  1  1/59 (1.69%) 
Renal tubular acidosis  1  1/59 (1.69%) 
Respiratory, thoracic and mediastinal disorders   
Tonsillar hypertrophy  1  1/59 (1.69%) 
Surgical and medical procedures   
Nephrectomy  1  1/59 (1.69%) 
Postoperative care  1  1/59 (1.69%) 
Vascular disorders   
Hypertension  1  1/59 (1.69%) 
1
Term from vocabulary, MedDRA 13.0
Indicates events were collected by systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cysteamine Bitartrate
Affected / at Risk (%)
Total   58/59 (98.31%) 
Blood and lymphatic system disorders   
Anaemia  1  4/59 (6.78%) 
Cardiac disorders   
Left ventricular hypertrophy  1  4/59 (6.78%) 
Eye disorders   
Conjunctivitis  1  14/59 (23.73%) 
Photophobia  1  3/59 (5.08%) 
Gastrointestinal disorders   
Vomiting  1  40/59 (67.80%) 
Diarrhoea  1  17/59 (28.81%) 
Nausea  1  16/59 (27.12%) 
Abdominal pain  1  12/59 (20.34%) 
Breath odour  1  8/59 (13.56%) 
Abdominal pain upper  1  7/59 (11.86%) 
Constipation  1  4/59 (6.78%) 
Abdominal discomfort  1  3/59 (5.08%) 
Dyspepsia  1  3/59 (5.08%) 
Flatulence  1  3/59 (5.08%) 
Gastrooesophageal reflux disease  1  3/59 (5.08%) 
General disorders   
Fatigue  1  10/59 (16.95%) 
Pyrexia  1  8/59 (13.56%) 
Asthenia  1  4/59 (6.78%) 
Influenza like illness  1  4/59 (6.78%) 
Oedema peripheral  1  3/59 (5.08%) 
Pain  1  3/59 (5.08%) 
Immune system disorders   
Seasonal allergy  1  3/59 (5.08%) 
Infections and infestations   
Influenza  1  14/59 (23.73%) 
Nasopharyngitis  1  13/59 (22.03%) 
Gastroenteritis  1  11/59 (18.64%) 
Ear infection  1  10/59 (16.95%) 
Upper respiratory tract infection  1  10/59 (16.95%) 
Sinusitis  1  6/59 (10.17%) 
Urinary tract infection  1  6/59 (10.17%) 
Bronchitis  1  5/59 (8.47%) 
Otitis media  1  5/59 (8.47%) 
Molluscum contagiosum  1  3/59 (5.08%) 
Pharyngitis  1  3/59 (5.08%) 
Pharyngitis streptococcal  1  3/59 (5.08%) 
Rhinitis  1  3/59 (5.08%) 
Tonsillitis  1  3/59 (5.08%) 
Varicella  1  3/59 (5.08%) 
Viral infection  1  3/59 (5.08%) 
Injury, poisoning and procedural complications   
Joint sprain  1  4/59 (6.78%) 
Arthropod bite  1  3/59 (5.08%) 
Investigations   
Blood creatinine increased  1  5/59 (8.47%) 
Metabolism and nutrition disorders   
Dehydration  1  6/59 (10.17%) 
Decreased appetite  1  5/59 (8.47%) 
Hypokalaemia  1  3/59 (5.08%) 
Musculoskeletal and connective tissue disorders   
Arthralgia  1  10/59 (16.95%) 
Pain in extremity  1  9/59 (15.25%) 
Back pain  1  4/59 (6.78%) 
Muscle spasms  1  3/59 (5.08%) 
Nervous system disorders   
Headache  1  22/59 (37.29%) 
Syncope  1  5/59 (8.47%) 
Lethargy  1  3/59 (5.08%) 
Psychiatric disorders   
Depression  1  5/59 (8.47%) 
Reproductive system and breast disorders   
Dysmenorrhoea  1  3/59 (5.08%) 
Respiratory, thoracic and mediastinal disorders   
Cough  1  10/59 (16.95%) 
Epistaxis  1  5/59 (8.47%) 
Oropharyngeal pain  1  5/59 (8.47%) 
Skin and subcutaneous tissue disorders   
Skin odour abnormal  1  6/59 (10.17%) 
Acne  1  3/59 (5.08%) 
Rash  1  3/59 (5.08%) 
Vascular disorders   
Hypertension  1  7/59 (11.86%) 
1
Term from vocabulary, MedDRA 13.0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Horizon requests that any investigator/institution that plans on presenting/publishing results provide written notification of their request 60 days prior to their presentation/publication. Horizon requests that no presentation/publication will be instituted until 12 months after a study is completed, or after the first presentation/publication whichever occurs first. A delay may be proposed of a presentation/publication if Horizon needs to secure patent or proprietary protection.
Results Point of Contact
Layout table for Results Point of Contact information
Name/Title: Evelyn Olson
Organization: Horizon Pharma USA, Inc.
Phone: 224-383-3000
EMail: clinicaltrials@horizonpharma.com
Layout table for additonal information
Responsible Party: Horizon Pharma USA, Inc.
ClinicalTrials.gov Identifier: NCT01197378     History of Changes
Other Study ID Numbers: RP103-04
2010-018365-34 ( EudraCT Number )
First Submitted: September 3, 2010
First Posted: September 9, 2010
Results First Submitted: June 26, 2018
Results First Posted: July 24, 2018
Last Update Posted: July 24, 2018