Modified Diet Trial: A Study of SMT C1100 in Paediatric Patients With DMD Who Follow a Balanced Diet

NCT ID: NCT02383511

Last Updated: 2015-08-26

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

12 participants

Study Classification

INTERVENTIONAL

Study Start Date

2015-02-28

Study Completion Date

2015-08-31

Brief Summary

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Placebo-controlled, multi-centre, randomized, double-blind dose escalation study. The aim is to evaluate the pharmacokinetics (PK) and safety of SMT C1100 in paediatric patients with Duchenne Muscular Dystrophy (DMD) who follow a balanced diet.

Detailed Description

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Primary Objective:

To determine the plasma concentration of SMT C1100 calculated at each time point for each subject (sample size (n), mean, standard deviation (SD), percentage of coefficient of variation (%CV), geometric mean, median, minimum, and maximum for the parent and the major metabolites).

Secondary Objectives:

1. To determine the safety and tolerability of single and multiple oral doses of SMT C1100 in patients with Duchenne Muscular Dystrophy (DMD) by assessing the participants adverse events, ECG results, vital signs and laboratory tests.
2. To evaluate the diurnal variability in the steady state PK of SMT C1100 calculated at each time point for each subject (sample size (n), mean, standard deviation (SD), percentage of coefficient of variation (%CV), geometric mean, median, minimum, and maximum for the parent and the major metabolites).
3. To evaluate reductions in creatine phosphokinase as a potential pharmacodynamic (PD) marker of SMT C1100 activity and clinical benefit.

Conditions

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Muscular Dystrophy, Duchenne

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Sequence 1

Drug: SMT C1100 or placebo 3-treatment (Period 1,2 and 3)

Group Type OTHER

SMT C1100

Intervention Type DRUG

Period 1, SMT C1100 1250 mg BID; Period 2, Placebo BID; Period 3, SMT C1100 2500 mg BID

Sequence 2

Drug: SMT C1100 or placebo 3-treatment (Period 1,2, and 3)

Group Type OTHER

SMT C1100

Intervention Type DRUG

Period 1, SMT C1100 1250 mg BID; Period 2, SMT C1100 2500 mg BID; Period 3, Placebo BID

Sequence 3

Drug: SMT C1100 or placebo 3-treatment (Period 1,2 and 3)

Group Type OTHER

SMT C1100

Intervention Type DRUG

Period 1, Placebo BID; Period 2, SMT C1100 1250 mg BID; Period 3, SMT C1100 2500 mg BID

Interventions

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SMT C1100

Period 1, SMT C1100 1250 mg BID; Period 2, Placebo BID; Period 3, SMT C1100 2500 mg BID

Intervention Type DRUG

SMT C1100

Period 1, SMT C1100 1250 mg BID; Period 2, SMT C1100 2500 mg BID; Period 3, Placebo BID

Intervention Type DRUG

SMT C1100

Period 1, Placebo BID; Period 2, SMT C1100 1250 mg BID; Period 3, SMT C1100 2500 mg BID

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

1. Patients will be males of any ethnic origin with a genetic diagnosis of DMD.
2. Children between 5 and 13 years of age.
3. A parent/legal guardian must date and sign a written consent on behalf of the patient, according to International Conference on Harmonisation (ICH) and local regulations. This person must understand the contents of the consent, requirements of the study and have had an opportunity to review questions with a medically trained member of the site study team.
4. The patient is willing to give verbal or written age appropriate assent to participate.
5. For safety reasons, the patient's parent/legal guardian must have a good understanding of the English language, which the consent/assent forms are available, and understand the requirements for reporting of any AE to the Investigator.
6. The patient has 6 months or more stable systemic (Patients using an intermittent regimen of steroid are allowed to be enrolled) corticosteroid therapy prior to Screening. Dose modifications for body weight are permitted.
7. The patient or parent is willing to adhere to a balanced diet from 1 week prior to dosing until the end of the follow-up period.
8. Patients must agree to not have sexual intercourse during the study treatment phases and until the end of their participation in the study.

Exclusion Criteria

1. Enrolment or participation in any therapeutic clinical trial within the prior 3 months or 5 times the half-life (whichever is longer). Prior exposure to SMT C1100 is NOT an exclusion criterion.
2. Known hypersensitivity to the excipients of the study drug or a previous history of drug allergy.
3. The patient or parent is unwilling to adhere to a balanced diet from 1 week prior to dosing until the end of the follow-up period.
4. Is dairy or lactose intolerant, has an allergy to egg or nuts or any other dietary restrictions that might interfere with the conduct of the study.
5. Is unable to refrain from eating cruciferous vegetables and barbecued (chargrilled) meat for the duration of the study.
6. Use of prohibited medication within 5 half-lives prior to baseline assessments, unless otherwise stated in protocol.
7. Need for mechanical ventilation.
8. The patient experiences intermittent or continuous difficulties in swallowing.
9. Non ambulatory.
10. Any clinically significant acute illness within 4 weeks of the start of dose administration.
11. Any comorbidity that, in the opinion of the Investigator, increases the risk of participating in the study.
12. Symptomatic cardiomyopathy that in the opinion of the Investigator prohibits participation in this study.
13. Abnormality in the 12-lead ECG at the Screening visit that, in the opinion of the Investigator, increases the risk of participating in the study.
14. Any clinically significant medical condition, other than DMD that in the opinion of the Investigator may increase the risk of participating in the study or interfere with the interpretation of safety or efficacy evaluations (e.g., concomitant illness, severe reflux, psychiatric condition or behavioural disorder).
15. The Patient smokes or has exposure to daily passive smoking (including parent/legal guardian, siblings) so as to minimise environmental factors causing CYP 1A induction.
16. Excessive exercise (Investigator opinion).
Minimum Eligible Age

5 Years

Maximum Eligible Age

13 Years

Eligible Sex

MALE

Accepts Healthy Volunteers

No

Sponsors

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Summit Therapeutics

INDUSTRY

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Locations

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Heart of England NHS Foundation Trust - Heart Lands Hospital

Birmingham, , United Kingdom

Site Status

Alder Hey Children's NHS Foundation Trust

Liverpool, , United Kingdom

Site Status

Great Ormond Street Hospital for Children NHS Foundation Trust

London, , United Kingdom

Site Status

Central Manchester University Hospitals NHS Foundation Trust- Royal Manchester Children's Hospital

Manchester, , United Kingdom

Site Status

Countries

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United Kingdom

References

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Ricotti V, Spinty S, Roper H, Hughes I, Tejura B, Robinson N, Layton G, Davies K, Muntoni F, Tinsley J. Safety, Tolerability, and Pharmacokinetics of SMT C1100, a 2-Arylbenzoxazole Utrophin Modulator, following Single- and Multiple-Dose Administration to Pediatric Patients with Duchenne Muscular Dystrophy. PLoS One. 2016 Apr 7;11(4):e0152840. doi: 10.1371/journal.pone.0152840. eCollection 2016.

Reference Type DERIVED
PMID: 27055247 (View on PubMed)

Other Identifiers

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SMT C11003

Identifier Type: -

Identifier Source: org_study_id

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