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

Aging Clinical Trial

Official title:

A Single (Part A) and Multiple (Part B) Dose Study of AMAZ-02, a Food Derived Ingredient to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamic Profile in Healthy Elderly Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02655393
• Other study ID #: 15.02.AMZ
• Secondary ID: OP095615.AMA - O
• Status: Completed
• Phase: Phase 1
• Start date: January 2016
• Est. completion date: December 2016

Study information

• Verified date: August 2022
• Source: Amazentis SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: December 2016
• Est. primary completion date: September 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 61 Years to 85 Years

Eligibility

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

Related Conditions & MeSH terms

• Aging
• Mitochondrial Dysfunction
• Muscle Function

Intervention

Dietary Supplement:
• Mitopure

Locations

Country	Name	City	State
France	Eurofins Optimed	Gières

Sponsors (2)

Lead Sponsor	Collaborator
Amazentis SA	Eurofins Optimed

Country where clinical trial is conducted

France, 

References & Publications (1)

Andreux PA, Blanco-Bose W, Ryu D, Burdet F, Ibberson M, Aebischer P, Auwerx J, Singh A, Rinsch C. The mitophagy activator urolithin A is safe and induces a molecular signature of improved mitochondrial and cellular health in humans. Nat Metab. 2019 Jun;1(6):595-603. doi: 10.1038/s42255-019-0073-4. Epub 2019 Jun 14. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Number of subjects with adverse events		6 weeks
Secondary	Plasma concentrations of AMAZ-02 and its metabolites over time and maximal plasma concentration (Cmax)		6 weeks
Secondary	Exposure to AMAZ-02 measured as area under the curve (AUC)		6 weeks
Secondary	Half-live (t 1/2) of AMAZ-02 and its metabolites		6 weeks
Secondary	Cmax of AMAZ-02 and its metabolites in urine		6 weeks
Secondary	AUC of AMAZ-02 and its metabolites in urine		6 weeks
Secondary	Gene expression for mitochondrial biomarkers in PBMC		6 weeks
Secondary	Gene expression for mitochondrial biomarkers in muscle tissue		6 weeks
Secondary	Blood Lipid Profile		6 weeks