Rimeporide in Patients With Duchenne Muscular Dystrophy

NCT02710591 | Completed Phase 1 Results DMC

• 2 other identifiers: EspeRare_RIM_0012015-002530-50
• Study Type: interventional
• Target: 20
• Locations: 4 countries
• Sites: 4

Brief Summary

In Duchenne Muscular Dystrophy (DMD) there is an imbalance between the levels of calcium and sodium in the muscles cells which is thought to be important in the damage which occurs overtime. Sodium/proton type 1 exchanger (NHE-1) inhibition is an innovative pathway that has proved to efficiently prevent the accumulation of muscle damage (inflammation and fibrosis) in animal models of muscular dystrophies and heart failure. Based on prior safety and efficacy results in animal and humans, NHE-1 inhibition with Rimeporide represents a new therapeutic approach with no restriction on age and on genetic subtypes which could be combined to other treatments that restore or augment dystrophin.This study examines the safety and tolerability and effects on the muscles of rimeporide, in patients aged 6 to 14 years with Duchenne Muscular Dystrophy (DMD).

Conditions

Muscular Dystrophy, Duchenne

Keywords

Rimeporide

Outcome Measures

Primary Outcomes (1)

• Number of Participants With Adverse Events

  Observations are given for the safety population (all patients who received at least one dose of study drug). Categorical data are presented with the number of subjects with at least one event for the following selections: * treatment-emergent AEs (TEAEs) * study drug-related TEAEs (ADRs) * serious TEAEs * study drug-related serious TEAEs (serious ADRs) * TEAEs leading to withdrawal * study drug-related TEAEs (ADRs) leading to withdrawal * serious TEAEs leading to withdrawal * TEAEs leading to death as outcome

  up to 6 weeks from first administration

Other Outcomes (1)

• PK Profile of Rimeporide - Cmax

  4 week study treatment

Study Arms (1)

Rimeporide

EXPERIMENTAL

Multiple oral doses of rimeporide ranging from 50 to 300 mg will be administered three times a day (TID) for a total of 4 weeks. 4 ascending dose levels will be studied sequentially in ascending order. Rimeporide is provided as hard gel 25 mg or 50 mg capsules. Each patient will participate in only 1 dose cohort. 5 patients are expected to be recruited in each cohort through all participating sites.

Drug: Rimeporide

Interventions

Rimeporide DRUG

Cohort 1: 50 mg TID in patients with a body weight ≤ 30kg at Baseline and 75 mg TID in patients with a body weight \> 30kg at Baseline Cohort 2: 100mg TID in patients with a body weight ≤ 30kg at baseline and 150 mg TID in patients with a body weight \> 30kg at Baseline Cohort 3: 150 mg TID in patients with a body weight ≤ 30kg at baseline and 200 mg TID in patients with a body weight \> 30kg at Baseline Cohort 4: 200 mg TID in patients with a body weight ≤ 30kg at Baseline and 300 mg TID mg TID in patients with a body weight \> 30kg at Baseline

Also known as: EMD 87580

Rimeporide

Eligibility Criteria

• Age: 6 Years - 14 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Duchenne muscular dystrophy genetically confirmed;
• Males between 6 and 14 years old;
• Able to walk independently at least 75 meters;
• Patients on a stable dose of corticosteroids at least 6 months prior to baseline;
• Patients able to swallow capsules size 4 according to the parents and investigator opinion;
• Willing and able to comply with all protocol requirements and procedures;
• Signed informed consents by the parent(s)/legal guardian(s);
• France only: Affiliated to or a beneficiary of a social security system

You may not qualify if:

• Patients with significant renal disease or impairment, with Glomerular Filtration Rate estimated using plasma cystatin C level using the Filler formula less than 90ml/min/1.73m2
• Current or history of liver disease or impairment,
• History of any significant medical disorder which may confound the interpretation of either efficacy or safety data e.g. inflammatory, coagulation disease, unstable cardiac or respiratory disease
• Acute illness within 4 weeks of the first administration of study medication which may interfere with study assessments;
• Significant change of dosage and/or dosing regimens for corticosteroids planned for the duration of study medication;
• Use of beta blockers / and ACEI or ARB unless at stable dose for at least 3 months prior to baseline;
• Use of Proton Pump Inhibitors unless at a stable dose for at least 3 months prior to baseline
• Use of aldosterone antagonists (i.e. spironolactone, eplerenone) within 3 months prior to first administration of study medication;
• Use of anticoagulants, antithrombotics or antiplatelet agents,
• Use of antibiotics with predominant renal secretion (e.g., cephalosporins), immunosuppressive agents exception corticosteroids, continuous treatment with non-steroidal, anti-inflammatory drugs (NSAIDs), or lithium;
• Previous treatment with idebenone or other forms of Coenzyme Q10 within 1 month of the first administration of study medication;
• Previous treatment with investigational drugs within 4 weeks (or 7 half-life if longer than 4 weeks) of the first administration of study medication including placebo;
• A baseline QTc\>450msec,or history of risk factors for torsades de pointes (eg, heart failure, hypokalaemia, family history of long QT syndrome);
• LVEF≤ 45% at screening or within the past 6 months and/or history of acute heart failure;
• Ventilator dependent;

Sponsors & Collaborators

• EspeRare Foundation: lead

Study Sites (4)

I-Motion - Hôpital Armand Trousseau

Paris, Île-de-France Region, 75012, France

Location

San Raffaele Hospital

Milan, 20132, Italy

Location

Santa Creu i Sant Pau Hospital

Barcelona, 08041, Spain

Location

UCL Institute of Child Health and Great Ormond Street Hospital

London, WC1N 1EH, United Kingdom

Location

Related Links

• Sponsor website

MeSH Terms

Conditions

Muscular Dystrophy, Duchenne

Interventions

N-(2-methyl-4,5-bis(methylsulfonyl)benzoyl)guanidine

Condition Hierarchy (Ancestors)

Muscular Dystrophies; Muscular Disorders, Atrophic; Muscular Diseases; Musculoskeletal Diseases; Neuromuscular Diseases; Nervous System Diseases; Genetic Diseases, X-Linked; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Results Point of Contact

• Title: Florence Porte-Thomé
• Organization: EspeRare Fondation

porte.florence@esperare.org

22 794 4004

Study Officials

• Florence Porte-Thomé

  R&D Director EspeRare

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 26, 2016
• First Posted: March 17, 2016
• Study Start: March 1, 2016
• Primary Completion: December 1, 2017
• Study Completion: February 1, 2018
• Last Updated: July 18, 2019
• Results First Posted: July 18, 2019

Record last verified: 2019-01

Data Sharing

• IPD Sharing: Will not share

Locations

IT (1); GB (1); ES (1); FR (1)