Trial Outcomes & Findings for Study of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet (NCT NCT00272792)

NCT ID: NCT00272792

Last Updated: 2015-08-13

Results Overview

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

45 participants

Primary outcome timeframe

at Week 10

Results posted on

2015-08-13

Participant Flow

In Part 1, subjects received Phenoptin for 8 days as part of their evaluation for Phenoptin responsiveness. Subjects who met response criteria were randomized 3:1 to Phenoptin or placebo for additional 10 weeks in Part 2, following a minimum 1-week wash-out period.

Participant milestones

Participant milestones
Measure
Sapropterin Dihydrochloride
Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Placebo
Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Part 1: Responsiveness
STARTED
90
0
Part 1: Responsiveness
COMPLETED
89
0
Part 1: Responsiveness
NOT COMPLETED
1
0
Part 2: Blinded, Placebo Control Period
STARTED
33
12
Part 2: Blinded, Placebo Control Period
COMPLETED
32
9
Part 2: Blinded, Placebo Control Period
NOT COMPLETED
1
3

Reasons for withdrawal

Reasons for withdrawal
Measure
Sapropterin Dihydrochloride
Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Placebo
Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Part 1: Responsiveness
Lost to Follow-up
1
0
Part 2: Blinded, Placebo Control Period
Withdrawal by Subject
0
2
Part 2: Blinded, Placebo Control Period
Lack of Efficacy
1
0
Part 2: Blinded, Placebo Control Period
Patient Uncooperative
0
1

Baseline Characteristics

Study of Phenoptin to Increase Phenylalanine Tolerance in Phenylketonuric Children on a Phenylalanine-restricted Diet

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Sapropterin Dihydrochloride
n=33 Participants
Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Placebo
n=12 Participants
Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Total
n=45 Participants
Total of all reporting groups
Age, Continuous
7.7 years
STANDARD_DEVIATION 2.8 • n=5 Participants
7.1 years
STANDARD_DEVIATION 2.0 • n=7 Participants
7.5 years
STANDARD_DEVIATION 2.6 • n=5 Participants
Sex: Female, Male
Female
13 Participants
n=5 Participants
6 Participants
n=7 Participants
19 Participants
n=5 Participants
Sex: Female, Male
Male
20 Participants
n=5 Participants
6 Participants
n=7 Participants
26 Participants
n=5 Participants
Race
Caucasian
33 Participants
n=5 Participants
11 Participants
n=7 Participants
44 Participants
n=5 Participants
Race
Hispanic
0 Participants
n=5 Participants
1 Participants
n=7 Participants
1 Participants
n=5 Participants

PRIMARY outcome

Timeframe: at Week 10

Outcome measures

Outcome measures
Measure
Sapropterin Dihydrochloride
n=33 Participants
Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Placebo
n=12 Participants
Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Amount of Dietary Supplemented Phenylalanine (Phe)Tolerated in Children With Phenylketonuria
20.9 mg/kg/day
Standard Deviation 15.4
2.9 mg/kg/day
Standard Deviation 4.0

SECONDARY outcome

Timeframe: Baseline to Week 3

Outcome measures

Outcome measures
Measure
Sapropterin Dihydrochloride
n=33 Participants
Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Placebo
n=12 Participants
Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Change in Phenylalanine Levels From Baseline to Week 3
-147.4 umol/L
Standard Error 29.0
-90.3 umol/L
Standard Error 48.3

Adverse Events

Sapropterin Dihydrochloride

Serious events: 0 serious events
Other events: 26 other events
Deaths: 0 deaths

Placebo

Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Sapropterin Dihydrochloride
n=33 participants at risk
Phenoptin, provided in tablets containing 100 mg of sapropterin dihydrochloride each, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4-8 oz (120-240 mL) of water or apple juice for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Placebo
n=12 participants at risk
Placebo, provided as tablets similar to Phenoptin tablets, was administered orally once daily in the morning as the number of tablets equivalent to a 20mg/kg/day dose dissolved in 4 8 oz (120-240 mL) of water or apple juice. for 6 weeks. A follow-up call or visit was made 4 weeks later during this double-blind, placebo-controlled study.
Injury, poisoning and procedural complications
Contusion
9.1%
3/33 • Number of events 3
8.3%
1/12 • Number of events 1
Injury, poisoning and procedural complications
Excoriation
6.1%
2/33 • Number of events 3
0.00%
0/12
Injury, poisoning and procedural complications
Thermal Burn
0.00%
0/33
8.3%
1/12 • Number of events 1
Infections and infestations
Streptococcal Infection
6.1%
2/33 • Number of events 2
16.7%
2/12 • Number of events 2
Infections and infestations
Upper Respiratory Tract Infection
6.1%
2/33 • Number of events 2
8.3%
1/12 • Number of events 1
Infections and infestations
Appendicitis
0.00%
0/33
8.3%
1/12 • Number of events 1
Infections and infestations
Conjuctivitis Infective
0.00%
0/33
8.3%
1/12 • Number of events 1
Infections and infestations
Rhinitis
0.00%
0/33
8.3%
1/12 • Number of events 1
Infections and infestations
Viral Infection
0.00%
0/33
8.3%
1/12 • Number of events 2
Respiratory, thoracic and mediastinal disorders
Rhinorrhea
21.2%
7/33 • Number of events 7
0.00%
0/12
Respiratory, thoracic and mediastinal disorders
Cough
15.2%
5/33 • Number of events 7
0.00%
0/12
Respiratory, thoracic and mediastinal disorders
Pharyngolaryngeal Pain
12.1%
4/33 • Number of events 5
8.3%
1/12 • Number of events 1
Respiratory, thoracic and mediastinal disorders
Nasal Congestion
9.1%
3/33 • Number of events 4
0.00%
0/12
Gastrointestinal disorders
Abdominal Pain
9.1%
3/33 • Number of events 6
8.3%
1/12 • Number of events 1
Gastrointestinal disorders
Diarrhoea
12.1%
4/33 • Number of events 5
0.00%
0/12
Gastrointestinal disorders
Vomiting
12.1%
4/33 • Number of events 4
0.00%
0/12
Gastrointestinal disorders
Toothache
6.1%
2/33 • Number of events 2
0.00%
0/12
Gastrointestinal disorders
Aphthous Stomatitis
0.00%
0/33
8.3%
1/12 • Number of events 1
Nervous system disorders
Headache
21.2%
7/33 • Number of events 7
8.3%
1/12 • Number of events 1
Skin and subcutaneous tissue disorders
Rash
3.0%
1/33 • Number of events 1
16.7%
2/12 • Number of events 4
Skin and subcutaneous tissue disorders
Erythema
6.1%
2/33 • Number of events 2
0.00%
0/12
Skin and subcutaneous tissue disorders
Prurigo
0.00%
0/33
8.3%
1/12 • Number of events 1
General disorders
Pyrexia
9.1%
3/33 • Number of events 3
16.7%
2/12 • Number of events 2
General disorders
Fatigue
3.0%
1/33 • Number of events 1
16.7%
2/12 • Number of events 2
Investigations
Neutrophil Count Decreased
3.0%
1/33 • Number of events 1
8.3%
1/12 • Number of events 1
Investigations
White Blood Cell Count Decreased
3.0%
1/33 • Number of events 1
8.3%
1/12 • Number of events 1
Blood and lymphatic system disorders
Lymphadenopathy
6.1%
2/33 • Number of events 2
0.00%
0/12
Metabolism and nutrition disorders
Decreased Appetite
6.1%
2/33 • Number of events 3
0.00%
0/12
Psychiatric disorders
Depression
0.00%
0/33
8.3%
1/12 • Number of events 1
Psychiatric disorders
Mood Swings
0.00%
0/33
8.3%
1/12 • Number of events 1

Additional Information

Medical Information Services

BioMarin Pharmaceutical Inc.

Phone: 1-800-983-4587

Results disclosure agreements

  • Principal investigator is a sponsor employee The first publication of the results shall be made by Sponsor in a joint publication. If such a multi-center publication is not submitted within 12 months after conclusion of the study, the PI may publish the results from their site individually, subject however to comply with the other terms of the agreement.
  • Publication restrictions are in place

Restriction type: OTHER