Study of ataluren in patients with Methylmalonic Acidemia

Phase 1

Conditions: onsense Mutation Methylmalonic Acidemia (MMA)
MedDRA version: 14.0Level: LLTClassification code 10064180Term: Blood methylmalonic acid increasedSystem Organ Class: 10022891 - Investigations
Therapeutic area: Diseases [C] - Congenital, Hereditary, and Neonatal Diseases and Abnormalities [C16]

Registration Number: EUCTR2009-016654-41-BE

Lead Sponsor: PTC Therapeutics, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 18

Inclusion Criteria

1. Evidence of signed and dated informed consent document(s) indicating that the subject (and/or a parent/legal guardian) has been informed of all pertinent aspects of the study. Note: If the study candidate is considered a child or is unable to give consent under local regulation, a parent or legal guardian must provide written consent prior to initiation of study screening procedures and the study candidate may be required to provide written assent. The rules of the responsible Institutional Review Board/Independent Ethic Committee (IRB/IEC) regarding whether one or both parents must provide consent and the appropriate ages for obtaining consent and assent from the subject should be followed.
2. Age =2 years at the start of study drug.
3. Phenotypic evidence of MMA based on the presence of characteristic clinical symptoms or signs and an elevated plasma MMacid level as specified in Table 1 of the protocol.
4. Documentation of the presence of a nonsense mutation in at least 1 allele of the MUT or MMAA (cblA) or MMAB (cblB) gene.
5. Verification that a blood sample has been drawn for sequencing of the relevant gene at a certified laboratory. Note: A subject who has written documentation of a nonsense mutation as the cause for MMA need not wait for confirmatory results to start ataluren as long as the confirmatory genotyping blood sample has been drawn.
This blood sample does not need to be obtained if the subject has written documentation of gene sequencing performed previously in the reference lab used in this study.
6. Confirmed screening laboratory values within the central laboratory ranges specified in Table 1 of the protocol. Note: Confirmation should be performed for out-of-range values to determine if the abnormality is real or artifactual. Values used to establish eligibility should be obtained within the screening period, and should generally be the most recent measurement.
7. Willingness, if not surgically sterile, to abstain from sexual intercourse or employ a barrier or medical method of contraception during ataluren administration and follow-up periods.
8. Willingness and ability to comply with scheduled visits, drug administration plan, study procedures, and study restrictions. Note: Psychological, social, familial, or geographical factors that might preclude adequate study participation should be considered.
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 3
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range 0

Exclusion Criteria

1. Known hypersensitivity to any of the ingredients or excipients of the study drug
(polydextrose, polyethylene glycol 3350, poloxamer 407, mannitol 25C, crospovidone XL10, hydroxyethyl cellulose, vanilla, colloidal silica, or magnesium stearate).
2. Any change (initiation, change in type of drug, dose modifications, schedule modifications, interruption, discontinuation or reinitiation) in chronic treatment for MMA (eg, cobalamin, L-carnitine, antibiotics for gut flora) within 2 months prior to start of Screening laboratory assessments.
3. Any change in prescribed diet, protein intake, or caloric intake within 2 months prior to start of Screening laboratory assessments.
4. Episode of metabolic decompensation within 1 month prior to start of Screening laboratory assessments.
5. Exposure to another investigational drug within 1 month prior to start of study drug.
6. Ongoing dialysis for renal dysfunction.
7. History of any form of organ transplantation or expectation that the patient may undergo organ transplantation during the planned study period.
8. Ongoing participation in any other therapeutic clinical trials.
9. Pregnancy or breast-feeding.
10. Ongoing warfarin, phenytoin or tolbutamide therapy.
11. Prior or ongoing medical condition (eg, concomitant illness, alcoholism, drug abuse, psychiatric condition), medical history, physical findings, ECG findings, or laboratory abnormality that, in the investigator’s opinion, could adversely affect the safety of the subject, makes it unlikely that the course of study drug administration or follow-up would be completed, or could impair the assessment of study results.