Trial Outcomes & Findings for Rimeporide in Patients With Duchenne Muscular Dystrophy (NCT NCT02710591)

Last Updated: 2019-07-18

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

20 participants

Primary outcome timeframe

up to 6 weeks from first administration

Results posted on

2019-07-18

Participant Flow

The recruitment period varied depending on the recruitment speed ; started in March 2016 to November 2017. it was competitive among the 4 sites: France, Spain, Italy and UK. A time interval of at least 1 week was maintained between adminstration of first dose in the first 3 patients of each cohort. It was extended to all patients for cohort 4.

Screening details: Screening was carried out within 4 week prior to first administration of Rimeporide (SD1) to enable confirmation of patient eligibility and following the signature of the Informed Consent Form.

Participant milestones

Participant milestones
Measure	Cohort 1 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 50 mg TID; patients with a body weight more than 30kg at baseline were administered 75 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 2 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 100 mg TID; patients with a body weight more than 30kg at baseline were administered 150 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 3 5 patients in total: patients with a with a body weight less than or equal to 30kg at baseline were administered 150 mg TID; patients with a body weight more than 30kg at baseline were administered 200 mg TID. Each patient received rimeporide during 4 weeks.	Cohort 4 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 200 mg TID; patients with a body weight more than 30kg at baseline were administered 300 mg TID. Each patient received rimeporide during 4 weeks
Overall Study STARTED	5	5	5	5
Overall Study COMPLETED	5	5	5	5
Overall Study NOT COMPLETED	0	0	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Rimeporide in Patients With Duchenne Muscular Dystrophy

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Cohort 1 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 50 mg TID; patients with a body weight more than 30kg at baseline were administered 75 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 2 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 100 mg TID; patients with a body weight more than 30kg at baseline were administered 150 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 3 n=5 Participants 5 patients in total: patients with a with a body weight less than or equal to 30kg at baseline were administered 150 mg TID; patients with a body weight more than 30kg at baseline were administered 200 mg TID. Each patient received rimeporide during 4 weeks.	Cohort 4 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 200 mg TID; patients with a body weight more than 30kg at baseline were administered 300 mg TID. Each patient received rimeporide during 4 weeks	Total n=20 Participants Total of all reporting groups
Age, Categorical <=18 years	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	20 Participants n=21 Participants
Age, Categorical Between 18 and 65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Age, Continuous	8.4 years STANDARD_DEVIATION 1.7 • n=5 Participants	8.2 years STANDARD_DEVIATION 1.5 • n=7 Participants	8.8 years STANDARD_DEVIATION 1.6 • n=5 Participants	9.2 years STANDARD_DEVIATION 0.4 • n=4 Participants	8.7 years STANDARD_DEVIATION 1.3 • n=21 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Sex: Female, Male Male	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	20 Participants n=21 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	5 Participants n=5 Participants	5 Participants n=7 Participants	5 Participants n=5 Participants	5 Participants n=4 Participants	20 Participants n=21 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United Kingdom	0 participants n=5 Participants	1 participants n=7 Participants	3 participants n=5 Participants	1 participants n=4 Participants	5 participants n=21 Participants
Region of Enrollment Italy	0 participants n=5 Participants	1 participants n=7 Participants	2 participants n=5 Participants	3 participants n=4 Participants	6 participants n=21 Participants
Region of Enrollment France	5 participants n=5 Participants	0 participants n=7 Participants	0 participants n=5 Participants	1 participants n=4 Participants	6 participants n=21 Participants
Region of Enrollment Spain	0 participants n=5 Participants	3 participants n=7 Participants	0 participants n=5 Participants	0 participants n=4 Participants	3 participants n=21 Participants

PRIMARY outcome

Timeframe: up to 6 weeks from first administration

Population: Observations are given for the safety population (all patients who received at least one dose of study drug).

Outcome measures

Outcome measures
Measure	Cohort 1 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 50 mg TID; patients with a body weight more than 30kg at baseline were administered 75 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 2 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 100 mg TID; patients with a body weight more than 30kg at baseline were administered 150 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 3 n=5 Participants 5 patients in total: patients with a with a body weight less than or equal to 30kg at baseline were administered 150 mg TID; patients with a body weight more than 30kg at baseline were administered 200 mg TID. Each patient received rimeporide during 4 weeks.	Cohort 4 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 200 mg TID; patients with a body weight more than 30kg at baseline were administered 300 mg TID. Each patient received rimeporide during 4 weeks
Number of Participants With Adverse Events Treatment emergent adverse events (TEAEs)	2 Participants	1 Participants	5 Participants	4 Participants
Number of Participants With Adverse Events Treatment emergent adverse drug reactions (ADRs)	0 Participants	0 Participants	0 Participants	2 Participants
Number of Participants With Adverse Events SAEs	0 Participants	0 Participants	1 Participants	0 Participants
Number of Participants With Adverse Events Serious ADRs	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events TEAEs leading to withdrawal	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events TEAEs leading to death	0 Participants	0 Participants	0 Participants	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: 4 week study treatment

PK samples were collected according to the following schedule: * At Day 1: for half of the patients: just before first administration, and one sample in each of the following time frames after the first dose: * 0.5 to 1h after dosing, * 1 to 2h after dosing, * 2.5 to 3.5h after dosing, * 6h after dosing * At Day 1: for the other half of the patients: just before first administration, and one sample in each of the following time frames after the second dose: * 0.5 to 1h after dosing, * 1 to 2h after dosing, * 2.5 to 3.5h after dosing, * 6h after dosing Finally, at week 4 (Day 28) after the last dose: * 0.5 to 1h after dosing, * 6h after dosing

Outcome measures

Outcome measures
Measure	Cohort 1 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 50 mg TID; patients with a body weight more than 30kg at baseline were administered 75 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 2 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 100 mg TID; patients with a body weight more than 30kg at baseline were administered 150 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 3 n=5 Participants 5 patients in total: patients with a with a body weight less than or equal to 30kg at baseline were administered 150 mg TID; patients with a body weight more than 30kg at baseline were administered 200 mg TID. Each patient received rimeporide during 4 weeks.	Cohort 4 n=5 Participants 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 200 mg TID; patients with a body weight more than 30kg at baseline were administered 300 mg TID. Each patient received rimeporide during 4 weeks
PK Profile of Rimeporide - Cmax Cmax at Day 1	1286 ng/mL Standard Deviation 568	1987 ng/mL Standard Deviation 650	3013 ng/mL Standard Deviation 730	3819 ng/mL Standard Deviation 743
PK Profile of Rimeporide - Cmax Cmax at Day 28	1361 ng/mL Standard Deviation 431	2077 ng/mL Standard Deviation 974	2817 ng/mL Standard Deviation 675	3909 ng/mL Standard Deviation 846

Adverse Events

Cohort 1

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Cohort 2

Serious events: 0 serious events

Other events: 1 other events

Deaths: 0 deaths

Cohort 3

Serious events: 1 serious events

Other events: 5 other events

Deaths: 0 deaths

Cohort 4

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Cohort 1 n=5 participants at risk 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 50 mg TID; patients with a body weight more than 30kg at baseline were administered 75 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 2 n=5 participants at risk 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 100 mg TID; patients with a body weight more than 30kg at baseline were administered 150 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 3 n=5 participants at risk 5 patients in total: patients with a with a body weight less than or equal to 30kg at baseline were administered 150 mg TID; patients with a body weight more than 30kg at baseline were administered 200 mg TID. Each patient received rimeporide during 4 weeks.	Cohort 4 n=5 participants at risk 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 200 mg TID; patients with a body weight more than 30kg at baseline were administered 300 mg TID. Each patient received rimeporide during 4 weeks
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Gastrointestinal disorders Vomitting	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.

Other adverse events

Additional Information

Florence Porte-Thomé

EspeRare Fondation

Phone: 22 794 4004

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Cohort 1 n=5 participants at risk 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 50 mg TID; patients with a body weight more than 30kg at baseline were administered 75 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 2 n=5 participants at risk 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 100 mg TID; patients with a body weight more than 30kg at baseline were administered 150 mg TID. Each patient received Rimeporide during 4 weeks.	Cohort 3 n=5 participants at risk 5 patients in total: patients with a with a body weight less than or equal to 30kg at baseline were administered 150 mg TID; patients with a body weight more than 30kg at baseline were administered 200 mg TID. Each patient received rimeporide during 4 weeks.	Cohort 4 n=5 participants at risk 5 patients in total: patients with a body weight less than or equal to 30kg at baseline were administered 200 mg TID; patients with a body weight more than 30kg at baseline were administered 300 mg TID. Each patient received rimeporide during 4 weeks
Injury, poisoning and procedural complications Fall	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Vascular disorders Flushing	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 2 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Respiratory, thoracic and mediastinal disorders Cough	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Respiratory, thoracic and mediastinal disorders Oropharyngeal pain	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Nervous system disorders Headache	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	40.0% 2/5 • Number of events 2 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	40.0% 2/5 • Number of events 3 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Nervous system disorders Presyncope	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Nervous system disorders Dizziness	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Ear and labyrinth disorders Tympanic membrane perforation	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
General disorders Chills	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
General disorders Pyrexia	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Gastrointestinal disorders Diarrhoea	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	40.0% 2/5 • Number of events 3 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Gastrointestinal disorders Abdominal pain upper	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 2 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Gastrointestinal disorders Vomiting	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Gastrointestinal disorders Mouth ulceration	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Skin and subcutaneous tissue disorders Urticaria	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Musculoskeletal and connective tissue disorders Pain in extremity	20.0% 1/5 • Number of events 2 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.
Infections and infestations Nasopharyngitis	0.00% 0/5 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	40.0% 2/5 • Number of events 2 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.	20.0% 1/5 • Number of events 1 • Treatment emergent adverse events were collected from first administration of the study drug up to 6 weeks.