Safety Study on the Effect of Eurartesim™ on QT/QTc Interval Compared to Riamet in Healthy Volunteers

NCT01103830 | Completed Phase 1

• 1 other identifier: ST3073-ST3074-DM-09-006
• Study Type: interventional
• Target: 287
• Locations: 1 country
• Sites: 1

Brief Summary

The aim of such a study is to evaluate the impact of a therapeutic dose of Eurartesim™ compared to Riamet®, after multiple dose administration for 3 days in healthy male and female subjects on electrocardiographic parameters.

Conditions

Malaria, Falciparum

Keywords

P. falciparum Malaria, Eurartesim, ACT

Outcome Measures

Primary Outcomes (1)

• QTcF interval (Fridericia's correction QT interval)

  Group 1,4 and 5 (Day -1: pre-dose, each hour till 13h post-dose. Day 1: pre-dose, 1, 2, 3, 4, 5, and 6 h post-dose. Day 3: pre-dose, each hour till 13h post-dose and then 24h). Group 2 (Day -2: pre-dose, each hour till 13h post-dose and then 24h. Day 3: pre-dose, each hour till 13h post-dose and then 24h). Group 3 and 6 (Day -1: pre-dose, each hour till 13h post-dose. Day 1: pre-dose, 1, 2, 3, 4, 6, 8, 12 and 24h post-dose. Day 3: pre-dose, pre-dose, each hour till 13h post-dose. Day 4: pre-dose, 1, 2, 3, 4, 6, 8, 12 and 24h post-dose).

  before study drugs administration, during the 24 hrs post first and third dose and during follow-up

Secondary Outcomes (5)

• Effect of Eurartesim™ administered in different food conditions, on ECG parameters

  before study drugs administration, during the 24 hrs post first and last dose and during follow-up

• Effect of food on bioavailability of Eurartesim™

  during the 24 hrs post first and last dose

• To evaluate differences in PK and ECG profiles according to posology scheme

  during the 24 hrs post first and last dose

• relationship within the Pk parameters of active substances and ECG parameters

  during the 24 hrs post first and last dose

• to asses general safety and tolerability of Eurartesim™

  during the treatment and follow-up period

Study Arms (6)

Group 1

EXPERIMENTAL

3 or 4 tablets of Eurartesim™, depending of body weight, (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day 1 to Day 3. Administration of Eurartesim will be in fed condition following a high-fat/low-Kcal meal.

Drug: Eurartesim™

Group 2

ACTIVE COMPARATOR

4 tablets of Riamet® on Day -1 evening, 4 tablets of Riamet® bid (with an interval of 12 ± 0.5 h), in the morning and in the evening of Day 1 and Day 2, 4 tablets of Riamet® in the morning of Day 3. Administration of Riamet® will be in fed condition following a high-fat/low-Kcal meal.

Drug: Riamet®

Group 3

OTHER

3 or 4 tablets of Eurartesim™ placebo, depending of body weight, (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day1 to Day 3. Administration will be in the morning, in fed condition, following a high-fat/low-Kcal meal 1 tablet of Izilox® (400 mg moxifloxacin) in fed condition following a high-fat/low-Kcal meal, on Day 4 morning.

Other: Placebo and finally Moxifloxacin

Group 4

EXPERIMENTAL

3 or 4 tablets of Eurartesim™, depending of body weight, (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day 1 to Day 3. Administration of Eurartesim will be in fed condition following a high-fat/high-Kcal meal.

Drug: Eurartesim™

Group 5

EXPERIMENTAL

3 or 4 tablets of Eurartesim™, depending of body weight, (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day 1 to Day 3. Administration of Eurartesim will be in fasting condition.

Drug: Eurartesim™

Group 6

OTHER

3 or 4 tablets of Eurartesim™ placebo, depending of body weight, (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day1 to Day 3. Administration will be in the morning, in fasting condition. 1 tablet of Izilox® (400 mg moxifloxacin) in fed condition following a high-fat/low-Kcal meal, on Day 4 morning.

Other: Placebo and finally Moxifloxacin

Interventions

Eurartesim™ DRUG

3 or 4 tablets of Eurartesim™ (40mg Dihydroartemisinin and 320 mg Piperaquine phosphate), depending of body weight (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day 1 to Day 3

Also known as: Dihydroartemisinin and Piperaquine combination therapy

Group 1

Riamet® DRUG

4 tablets of Riamet® (20mg artemether/120mg lumefantrine) on Day -1 evening, 4 tablets of Riamet® bid (with an interval of 12 ± 0.5 h), in the morning and in the evening of Day 1 and Day 2, 4 tablets of Riamet® in the morning of Day 3.

Also known as: artemether and lumefantrine combination therapy

Group 2

Placebo and finally Moxifloxacin OTHER

3 or 4 tablets of Eurartesim™ placebo, depending of body weight, (3 tablets for subjects weighting less than 75 kg, 4 tablets for subjects weighting 75 kg or more), once daily from Day1 to Day 3. 1 tablet of Izilox® (400 mg moxifloxacin) on Day 4 morning.

Also known as: moxifloxacin

Group 3

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Male or female Caucasian subject ≥ 18 and ≤ 50 years;
• Good general health (by medical history and physical examination);
• For male and female subjects of childbearing potential use a double contraception method;
• For female subjects of childbearing potential only: negative plasma pregnancy test at Screening and at admission in the clinical unit;
• Body mass index (BMI) ≥18 and ≤ 27 kg/m2;
• No clinically relevant abnormalities in blood pressure and heart rate;
• No clinically relevant abnormalities in 12-lead ECG results;
• No clinically relevant abnormalities in results of laboratory tests;
• Registered with the French Social Security in agreement with the French law on biomedical experimentation.

You may not qualify if:

• A predictable poor compliance or inability to communicate well with the Investigator;
• Unsuitable veins for repeated venipuncture.
• Evidence of clinically relevant cardiovascular, renal, hepatic, hematological, gastrointestinal, pulmonary, metabolic-endocrine, neurological, urogenital or psychiatric diseases as judged by the Investigator;
• A history of additional risk factors for Torsades des Pointes (e.g., heart failure, hypokalemia, family history of Long QT Syndrome);
• The use of concomitant medications that prolong the QT/QTc interval;
• Any condition requiring regular concomitant medication, including herbal products and over-the-counter (OTC) medication or predicted need of any concomitant medication during the study;
• Evidence of any clinically significant acute or chronic disease, including known or suspected HIV, hepatitis B virus (HBV) and HCV infection;
• History of relevant clinical allergic reactions of any origin;
• Known hypersensitivity to any of the test materials or related compounds;
• Intake of any medication (except paracetamol, hormonal contraceptives and hormone replacement therapy for postmenopausal women), including OTC medications and herbal products that could affect the outcome of the study, within 2 weeks prior to the first drug administration or less than 5 times the t1/2 of that drug, whichever is the longer;
• Drug abuse;
• Current use of nicotine containing products and the inability to stop using nicotine containing products during confinement in the clinical centre.
• Use of caffeine containing beverages exceeding 500 mg caffeine/day and the inability to refrain from the use of caffeine containing beverages during confinement in the clinical centre;
• Intake of any food or any beverage containing grapefruit or grapefruit juice, orange or pomelo juice within 48 h prior to the first dosing and the inability to stop such intake during the study;
• Blood donation or loss of significant amount of blood within three months prior to the first dosing;

Sponsors & Collaborators

• sigma-tau i.f.r. S.p.A.: lead
• Medicines for Malaria Venture: collaborator

Study Sites (1)

SGS aster s.a.s

Paris, 75015, France

Location

Related Publications (1)

• Funck-Brentano C, Bacchieri A, Valentini G, Pace S, Tommasini S, Voiriot P, Ubben D, Duparc S, Evene E, Felices M, Corsi M. Effects of Dihydroartemisinin-Piperaquine Phosphate and Artemether-Lumefantrine on QTc Interval Prolongation. Sci Rep. 2019 Jan 28;9(1):777. doi: 10.1038/s41598-018-37112-6.

  PMID: 30692558 DERIVED

MeSH Terms

Conditions

Malaria, Falciparum

Interventions

artenimol; Artemether; Moxifloxacin

Condition Hierarchy (Ancestors)

Malaria; Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Lionel Hovsepian, MD

  SGS Aster S.A.S.

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY

Study Record Dates

• First Submitted: April 12, 2010
• First Posted: April 15, 2010
• Study Start: February 1, 2010
• Primary Completion: August 1, 2010
• Study Completion: December 1, 2010
• Last Updated: June 17, 2011

Record last verified: 2011-06

Locations

FR (1)