A Phase 1b Study of SMT C1100 in Subjects With Duchenne Muscular Dystrophy (DMD)

Duchenne Muscular Dystrophy Clinical Trial

Official title:

SMT C1100 - A Phase 1b, Open-label, Single and Multiple Oral Dose, Safety, Tolerability and Pharmacokinetic Study in Paediatric Patients With Duchenne Muscular Dystrophy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02056808
• Other study ID #: SMT C11002
• Status: Completed
• Phase: Phase 1
• First received: November 21, 2013
• Last updated: August 26, 2014
• Start date: November 2013
• Est. completion date: July 2014

Study information

• Verified date: August 2014
• Source: Summit Therapeutics
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to determine whether increasing doses of SMT C1100 are safe, well tolerated and achieve appropriate blood levels in patients with Duchenne Muscular Dystrophy (DMD).

Description:

Primary Objective: To determine the safety and tolerability of single and multiple oral doses of SMT C1100 in patients with Duchenne Muscular Dystrophy (DMD).

Secondary Objectives: To determine the single and multiple oral dose pharmacokinetics of SMT C1100 and its metabolites in patients with DMD.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 12
• Est. completion date: July 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: No
• Gender: Male
• Age group: 5 Years to 11 Years

Eligibility

Inclusion Criteria:

• Patients will be males of any ethnic origin with a genetic diagnosis of DMD.

• Children between 5 and 11 years of age.

• 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.

• The patient is willing to give verbal or written age appropriate assent to participate.

• For safety reasons, the patient's parent/legal guardian must have a good understanding of the English language, as this is the only language the consent/assent forms are written in, and understand the requirements for reporting of any adverse event to the Investigator.

Exclusion Criteria:

• Enrollment or participation in any therapeutic clinical trial within the prior 3 months or 5 times the half-life (whichever is longer).

• Initiation or change (other than dose modifications for body weight) of systemic corticosteroid therapy within 2 months prior to the start of dose administration or discontinuation of corticosteroids within 30 days prior to the start of dose administration.

• Known hypersensitivity to the excipients of the study drug or a previous history of drug allergy.

• Use of the following therapies is prohibited during the study and for at least 5 half-lives prior to the start of dose administration: Inducers of cytochrome P450 CYP1A2 (eg, carbamazepine, phenytoin, primidone, rifampin, omeprazole, and barbiturates), and moderate and strong inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin, enoxacin, mexiletine; propafenone, zileuton). Substrates of CYP1A2 with narrow therapeutic windows (e.g., tacrine, theophylline, methadone, mexiletine). Nicotine, including exposure to daily passive smoking to minimize cytochrome P450 CYP 1A induction. Chargrilled food, cruciferous vegetables, caffeine, tea, and any xanthine containing foods, and drinks are prohibited from 36 hours prior to check-in until final discharge from study. Herbal supplements and homeopathic preparations (unless approved by medical monitor).

• Need for mechanical ventilation.

• Non ambulatory.

• Any clinically significant acute illness within 4 weeks of the start of dose administration.

• Any co-morbidity that, in the opinion of the Investigator, increases the risk of participating in the study.

• Symptomatic cardiomyopathy that in the opinion of the Investigator prohibits participation in this study.

• Abnormality in the 12-lead ECG that, in the opinion of the Investigator, increases the risk of participating in the study.

• 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, psychiatric condition or behavioral disorder).

• Exposure to daily passive smoking (including parent/legal guardian, siblings) so as to minimize environmental factors causing cytochrome P450 CYP 1A induction. For information SMT C1100 is metabolized by cytochrome P450 CYP 1A.

• Excessive exercise (Investigator opinion).

Study Design

Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Duchenne Muscular Dystrophy
• Muscular Dystrophies
• Muscular Dystrophy, Duchenne

Intervention

Drug:
• SMT C1100
Comparison of safety and pharmacokinetic of different dosages of drug

Locations

Country	Name	City	State
United Kingdom	Heart of England NHS Foundation Trust - Heart Lands Hospital	Birmingham
United Kingdom	Alder Hey Children's NHS Foundation Trust	Liverpool
United Kingdom	Great Ormond Street for Children NHS Foundation Trust	London
United Kingdom	Central Manchester University Hospitals NHS Foundation Trust- Royal Manchester Children's Hospital	Manchester

Sponsors (1)

Lead Sponsor	Collaborator
Summit Therapeutics

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Safety and tolerability	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.	After 10 days of treatment phase	Yes
Secondary	Pharmacokinetic parameters at different dose levels	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.	After single oral dose and after 10 days of treatment phase	No