A Single and Multiple Dose Study of AMAZ-02 to Evaluate Safety and Pharmacokinetics in Elderly Subjects

Phase 1

Completed

• Conditions: Mitochondrial Dysfunction; Muscle Function; Aging
• Interventions: Dietary Supplement: Mitopure

• Registration Number: NCT02655393
• Lead Sponsor: Amazentis SA

Brief Summary

Part A:

The study is a double-blind, randomized, single ascending doses, study in 24 healthy elderly male and female volunteers. Each subject will be randomized for two subsequent doses in three cohorts.

Part B:

The study is a double-blind, randomized, multiple ascending doses study in 36 healthy elderly male and female volunteers. Subjects will be randomized to receive study product or placebo for 28 days.

Detailed Description

Part A: Single Ascending Dose study of AMAZ-02 with 3 cohorts (each cohort n=8 subjects, total n=24 subjects). Cohorts undergo two periods of single dose intervention separated by 3 week washout. Adverse events, clinical biochemistry for safety assessment and plasma and urine collected for pharmacokinetic measurement for parent and metabolite levels in circulation.

Part B: Multiple Ascending Dose study with 3 cohorts (each cohort n=12 subjects, total n=36 subjects). 28 day administration with AMAZ-02 for safety, PK and PD assessment.

Study Timeline

• Study Start: 2016-01
• Study First Submitted: 2016-01-08
• Study First Submitted QC: 2016-01-12
• Study First Posted: 2016-01-14
• Primary Completion: 2016-09
• Study Completion: 2016-12
• Status Verified: 2022-08
• Last Update Submitted: 2022-08-23
• Last Update Posted: 2022-08-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 60

Inclusion Criteria

1. Healthy male and female elderly subject, aged between 61 and 85 years inclusive;

2. Non-smoker subject or smoker of not more than 5 cigarettes a day;

3. Body Mass Index (BMI) between 18 and 32 kg/m2 inclusive;

4. Certified as healthy by a comprehensive clinical assessment (detailed medical history and complete physical examination);

5. Normal Blood Pressure (BP) and Heart Rate (HR) at the screening visit after 10 minutes in supine position:

   • 95 mmHg ≤ Systolic Blood Pressure (SBP) ≤ 160 mmHg,
   • 50 mmHg ≤ Diastolic Blood Pressure (DBP) ≤ 95 mmHg,
   • 50 bpm < HR < 80 bpm,
   • Or considered NCs by investigators;

6. Normal ECG recording on a 12-lead ECG at the screening visit:

   • 120 < PR < 220 ms,
   • QRS < 120 ms,
   • QTcf < 430 ms for male and < 450 ms for female,
   • No sign of any trouble of sinusal automatism,
   • Or considered NCS by investigators;

7. Laboratory parameters within the normal range of the laboratory (haematological, blood chemistry tests, urinalysis). Individual values out of the normal range can be accepted if judged clinically non relevant by the Investigator;

8. Normal dietary habits;

9. Demonstrate sedentary behaviour defined as having an activity category of 1 as assessed by the International Physical Activity Questionnaire (IPAQ). Activity level is < 600 MET (metabolic equivalent unit - minutes per week and limited to light intensity activities.

10. Accept to refrain consuming certain foods and supplements at least two weeks before inclusion.

11. Comprehension of the nature and purpose of the study and ability to communicate in person and by telephone in a manner that allows all protocol procedures to be carried out safety and reliably in the opinion of the investigative site staff

12. Ability to take up to 8 capsules of study medication

13. Signing a written informed consent prior to selection;

14. Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.

Exclusion Criteria

1. Any history or presence of cardiovascular, pulmonary, gastro-intestinal, hepatic, renal, metabolic, hematological, neurologic, psychiatric, systemic or infectious disease;
2. Frequent headaches and / or migraine, recurrent nausea and / or vomiting;
3. Symptomatic hypotension whatever the decrease of blood pressure or asymptomatic postural hypotension defined by a decrease in SBP or DBP equal to or greater than 20 mmHg within two minutes when changing from the supine to the standing position;
4. Blood donation (including in the frame of a clinical trial) within 2 months before administration;
5. General anaesthesia within 3 months before administration;
6. Presence or history of drug hypersensitivity, or allergic disease diagnosed and treated by a physician;
7. Lactose intolerance, milk protein or soy allergy.
8. Inability to abstain from intensive muscular effort;
9. No possibility of contact in case of emergency;
10. Use of any of the prohibited medications as detailed in the concomitant medication section
11. History or presence of drug or alcohol abuse (alcohol consumption > 40 grams / day);
12. Excessive consumption of beverages with xanthine bases (> 4 cups or glasses / day);
13. Positive Hepatitis B surface (HBs) antigen or anti Hepatitis C Virus (HCV) antibody, or positive results for Human Immunodeficiency Virus (HIV) 1 or 2 tests;
14. Positive results of screening for drugs of abuse;
15. Subject who, in the judgment of the Investigator, is likely to be non-compliant or uncooperative during the study, or unable to cooperate because of a language problem, poor mental development;
16. Exclusion period of a previous study;
17. Administrative or legal supervision;
18. Subjects should not have participated in previous clinical trials in the last 3 months and received compensation beyond a certain approved and predefined limit

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
Mitopure 2000 mg single dose	Mitopure	single dose of Mitopure soft gel capsules at 2000 mg dose, n=8 subjects (6 Active, 2 Placebo)
Mitopure 1000 mg multiple 28 day dose	Mitopure	Repeated 28 day dosing of Mitopure soft gel capsules at 1000 mg dose, n=12 subjects (9 Active, 3 Placebo)
Mitopure 250 mg multiple dose	Mitopure	Repeated 28 day dosing of Mitopure soft gel capsules at 250 mg dose, n=12 subjects (9 Active, 3 Placebo)
Mitopure 1000 mg single dose	Mitopure	single dose of Mitopure soft gel capsules at 1000 mg dose, n=8 subjects (6 Active, 2 Placebo)
Mitopure 500 mg multiple 28 day dose	Mitopure	Repeated 28 day dosing of Mitopure soft gel capsules at 500 mg dose, n=12 subjects (9 Active, 3 Placebo)
Mitopure 250 mg single dose	Mitopure	single dose of Mitopure soft gel capsules at 250 mg dose, n=8 subjects (6 Active, 2 Placebo)
Mitopure 500 mg single dose-Food Effect	Mitopure	single dose of Mitopure admixed in yoghurt at 500 mg dose, n=8 subjects (6 Active, 2 Placebo)
Mitopure 500 mg single dose	Mitopure	single dose of Mitopure soft gel capsules at 500 mg dose, n=8 subjects (6 Active, 2 Placebo)
Mitopure 1000 mg single dose-Food Effect	Mitopure	single dose of Mitopure admixed in yoghurt at 1000 mg dose, n=8 subjects (6 Active, 2 Placebo)

Primary Outcome Measures

Name	Time	Method
Number of subjects with adverse events	6 weeks

Secondary Outcome Measures

Name	Time	Method
Exposure to AMAZ-02 measured as area under the curve (AUC)	6 weeks
Gene expression for mitochondrial biomarkers in muscle tissue	6 weeks
Gene expression for mitochondrial biomarkers in PBMC	6 weeks
Blood Lipid Profile	6 weeks
Cmax of AMAZ-02 and its metabolites in urine	6 weeks
AUC of AMAZ-02 and its metabolites in urine	6 weeks
Plasma concentrations of AMAZ-02 and its metabolites over time and maximal plasma concentration (Cmax)	6 weeks
Half-live (t 1/2) of AMAZ-02 and its metabolites	6 weeks

Trial Locations

Locations (1)

Eurofins Optimed; 🇫🇷 Gières, France