Clinical Trial of Sodium Phenylbutyrate in Children With Spinal Muscular Atrophy Type I

• Register: ClinicalTrials.gov
• Last refreshed on: 19 October 2017
• Main ID: NCT00439218
• Date of registration: 22/02/2007
• Prospective Registration: Yes
• Primary sponsor: Westat
• Public title: Clinical Trial of Sodium Phenylbutyrate in Children With Spinal Muscular Atrophy Type I NPTUNE 02
• Scientific title: Phase I/IIa Clinical Trial of Sodium Phenylbutyrate in Pediatric Subjects With Type I Spinal Muscular Atrophy
• Date of first enrolment: January 2008
• Target sample size: 5
• Recruitment status: Terminated
• URL: https://clinicaltrials.gov/show/NCT00439218
• Study type: Interventional
• Phase: Phase 1/Phase 2

Countries of recruitment

United States

Contacts

• Name: René Gonin, PhD
• Affiliation: Mathematical Statistician, Westat

• Name: Peter R Gilbert, ScM
• Affiliation: The National Institute of Neurological Disorders and Stroke

Key inclusion & exclusion criteria

Inclusion Criteria:

Subjects must meet all of the following inclusion criteria within 14 days prior to
receiving the first dose of study drug.

- Weakness and hypotonia consistent with a clinical diagnosis of spinal muscular atrophy
(SMA) type I

- Laboratory documentation of homozygous absence of SMN1 exon 7

- Older than two months of age, but younger than 48 months of age, at the time of
enrollment. If the subject is older than 24 months of age at the time of enrollment,
the subject must require ventilatory support for at least 6 hours/day.

- Written informed consent of parents/guardian

- Weight greater than or equal to 7 kilograms

- Laboratory results drawn within 14 days prior to start of study drug demonstrating:
Hemoglobin within normal range at the clinical site; White Blood Cell Count =
3000/mm³; Platelet Count = 75,000/mm³; Lipase and Amylase = 1.5 x upper limit of
normal (ULN) in the absence of associated clinical symptoms; AST and ALT =2.5x ULN;
Bilirubin = 1.5x ULN in the absence of associated clinical symptoms; Sodium = 130 and
= 150 mmol/L; Potassium =3.0 and = 5.5 mmol/L; Chloride = 110 mmol/L; Calcium = 8.0
mg/dL; Bicarbonate = 16 mmol/L; Glucose = 55 and = 160 mg/dL; BUN = 39 mg/dL;
Creatinine = 1.5 x ULN

- Subjects who are on ventilators may enroll in the protocol providing they have been on
stable ventilator settings for at least the prior two weeks.

- Subject is expected to survive for at least 6 months following study entry

Exclusion Criteria:

Subjects who meet any of the following criteria will be excluded from participating in the
study:

- Evidence of renal dysfunction, blood dyscrasia, hepatic insufficiency, symptomatic
pancreatitis, cardiac arrhythmia, congenital heart defect, known history of metabolic
acidosis, hypertension, significant central nervous system impairment, or
neurodegenerative or neuromuscular disease other than SMA.

- Any adverse event = Grade 3 at the time of screening based on the protocol toxicity
grading table

- Any acute co-morbid condition interfering with the well-being of the subject within 7
days of enrollment including bacterial infection, viral infectious process, food
poisoning, temperature > 99.0ºF, need for acute treatment or observation due to any
other reason, as judged by the investigator.

- = Grade 2 vomiting;

- = Grade 2 liver dysfunction/failure (clinical);

- Any abnormality noted on EKG except for asymptomatic sinus arrhythmia

- History of allergy/sensitivity to sodium phenylbutyrate

- Use of sodium phenylbutyrate within 30 days of study entry

- Serious illness requiring systemic treatment and/or hospitalization within 14 days
prior to study entry (Subjects are not eligible following serious illness until
therapy is complete and the subject is stable, or until the subject is on therapy and
stable for at least 14 days.)

- Poor respiratory status which is expected to require the initiation of BiPAP during
the initial 29 days of drug administration.

- Use of medications intended for the treatment of SMA including riluzole, valproic
acid, hydroxyurea, oral use of albuterol, sodium phenylbutyrate, butyrate derivatives,
creatine, carnitine, growth hormone, anabolic steroids, probenecid, oral or parenteral
use of corticosteroids at entry, haloperidol, agents anticipated to increase or
decrease muscle strength or agents with known or presumed histone deacetylase (HDAC)
inhibition within 30 days prior to study entry.

Notes: Subjects who use a nebulizer or require an inhaler to receive albuterol will be
allowed in the study; however oral use of albuterol is prohibited. Topical use of steroids
will be allowed. Oral use of steroids is not allowed at entry, but these may be used as
clinically indicated while on study. Event grading will be based on the toxicity-grading
table in the protocol.



Age minimum: 2 Months
Age maximum: 48 Months
Gender: All

Health Condition(s) or Problem(s) studied

Spinal Muscular Atrophy Type I

Intervention(s)

Drug: sodium phenylbutyrate

Primary Outcome(s)

Survival Motor Neuron (SMN) Messenger Ribonucleic Acid (mRNA) [Time Frame: Baseline - 12 weeks]

Dose Limiting Toxicities (DLT) [Time Frame: 29 days]

Survival Motor Neuron (SMN) Protein [Time Frame: Baseline - 12 Weeks]

Secondary Outcome(s)

Drug Safety [Time Frame: 14 weeks]

Overall Study Drug Compliance [Time Frame: 12 weeks]

Pharmacokinetic Parameters (Maximum Plasma Concentration) [Time Frame: 12 weeks]

Pharmacokinetic Parameters (Time to Maximum Plasma Concentration) [Time Frame: 12 weeks]

Pharmacokinetic Parameters (Area Under the Plasma Concentration Versus Time Curve (AUC)) [Time Frame: 12 weeks]

Secondary ID(s)

N01NS42361_NPTUNE02

HHSN265200423611C

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

National Institute of Neurological Disorders and Stroke (NINDS)

Results

• Results available: Yes
• Date Posted: 20/07/2010
• URL: https://clinicaltrials.gov/ct2/show/results/NCT00439218