RI Study to Assess and Compare the Pharmacokinetic Parameters of MD1003 in Renal Impaired Patients and Healthy Subjects

NCT04252430 | Terminated Phase 1

• 2 other identifiers: MD1003CT2019602RI2019-002315-26
• Study Type: interventional
• Target: 24
• Locations: 2 countries
• Sites: 5

Brief Summary

This is a Phase 1, multicentric, open-label,two arms to assess and compare the effect of single oral administration of MD1003 on the pharmacokinetic parameters in renal impaired patients and healthy subjects with normal renal function. The planned enrollment is 36 subjects (18 impaired patients and 18 healthy subjects).

Conditions

Healthy Volunteers; Impaired Renal Function

Outcome Measures

Primary Outcomes (6)

• Area under curve from dosing time to last measurment (AUC (0-t)) for MD1003

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Area under curve from dosing tme to infinity (AUC(0-∞)) for MD1003

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Maximum plasma drug concentration (Cmax) for MD1003

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Measurement of concentration of MD1003

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Measurement of concentration of Bisnorbiotin

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Measurement of concentration of Biotin sulfoxide

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

Secondary Outcomes (23)

• Plasma pharmacokinetics: elimination half-life (t1/2) for MD1003

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Plasma pharmacokinetics: elimination half-life (t1/2) for Bisnorbiotin

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Plasma pharmacokinetics: elimination half-life (t1/2) for Biotin sulfoxide

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Plasma pharmacokinetics: time for maximum plasma concentration (tmax) for MD1003

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

• Plasma pharmacokinetics: time for maximum plasma concentration (tmax) for Bisnorbiotin

  predose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 18, 24, 36, 48, 72, 96, 120, 144, 168, 216, 264, 312 and 360 hours post-dose.

Study Arms (2)

Patients with renal impaired function

ACTIVE COMPARATOR

6 patients with mild renal impaired function, 6 patients with moderate renal impaired function and 6 patients with severe ranal impaired function

Drug: MD1003

Healthy subjects

ACTIVE COMPARATOR

Healthy volunteers will be matched with impaired renal function patients

Drug: MD1003

Interventions

MD1003 DRUG

Single oral dose administration of MD1003 at Day 1

Healthy subjects; Patients with renal impaired function

Eligibility Criteria

• Age: 18 Years - 75 Years
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects, aged 18 to 75 years inclusive
• Females participating in this study must be of non-childbearing potential or using highly effective contraception for the full duration of the study and for 1 month after the end of treatment, as described below:
• Cessation of menses for at least 12 months due to ovarian failure;
• Surgical sterilization such as bilateral oophorectomy, hysterectomy, or medically documented ovarian failure;
• Using an highly effective non-hormonal method of contraception (bilateral tubal occlusion, vasectomized partner or intra-uterine device);
• Negative serum pregnancy test at screening (if applicable);
• Normal hepatic function;
• Non-smoker subject or smoker of not more than 5 cigarettes a day;
• Signing a written informed consent prior to selection;
• Covered by Health Insurance System and / or in compliance with the recommendations of National Law in force relating to biomedical research.
• For renal impaired patients:
• Renal impairment patients with mild decrease in estimated creatinine clearance (CLcr) (60 ≤ CLcr ≤ 89 mL.min) or with moderate decrease of CLcr (30 ≤ CLcr ≤ 59 mL.min) or severe decrease of CLcr (15 ≤ CLcr ≤ 29 mL.min) using the Cockcroft-Gault equation;
• Supine blood pressure ≤ 170/110 mmHg;
• Documented renal impairment indicated by reduced estimated creatinine clearance within 12 months of screening or longer;
• Stable renal function as evidenced by ≤ 30% difference in two evaluation of estimated creatinine clearance on two separate occasions separated by at least 28 days with one measurement being the value at screening;

You may not qualify if:

• 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);
• History or presence of drug or alcohol abuse (alcohol consumption \> 40 grams/day);
• Subject/Patient 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;
• Subject/Patient who cannot be contacted in case of emergency;
• History or presence of allergy or unusual reactions to some drugs or anesthetics or known hypersensitivity to the investigation product or its excipients (including lactose intolerance);
• Any medications intake within 3 months that may interfere with absorption, distribution, metabolism or excretion of the study drug, or any medication that may result in induction or inhibition of microsomal enzymes;
• Administrative or legal supervision;
• Blood donation (including in the frame of a clinical trial) within 2 months before administration or blood donation planned during the study or within 2 months following participation to the study;
• Subject/Patient who is pregnant or breastfeeding. Subject/Patient should not be enrolled if she plans to become pregnant during the time of study participation;
• Excessive consumption of beverages with xanthine bases (\> 4 cups or glasses / day);
• Positive results of screening for drugs of abuse;
• Intake of any food or any beverage containing grapefruit or grapefruit juice within 48h prior to the first dosing and the inability to stop such intake during the study;
• Evidence or history of clinically significant uncontrolled hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, hepatic, psychiatric, neurologic, metabolic, systemic, infectious, or allergic disease (including drug hypersensitivity or allergies, but excluding untreated, asymptomatic, seasonal allergies at time of dosing);
• General anesthesia within 3 months before administration;
• For renal impaired patients:

Sponsors & Collaborators

• MedDay Pharmaceuticals SA: lead
• Eurofins Optimed: collaborator

Study Sites (5)

Eurofins Optimed

Gières, 38610, France

Location

DRC Drug Research Center Ltd.

Balatonfüred, 8231, Hungary

Location

Semmelweis University Faculty of Medicine

Budapest, 1083, Hungary

Location

University of Debrecen Medical and Health Center

Debrecen, 4032, Hungary

Location

Clinical Research Units Hungary Ltd.

Miskolc, 3528, Hungary

Location

MeSH Terms

Conditions

Renal Insufficiency

Condition Hierarchy (Ancestors)

Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Study Officials

• Yves Donazzolo, MD

  Eurofins Optimed

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: Open label, Parallel-group, Single oral dose

Study Record Dates

• First Submitted: January 31, 2020
• First Posted: February 5, 2020
• Study Start: October 9, 2019
• Primary Completion: March 17, 2020
• Study Completion: March 17, 2020
• Last Updated: May 13, 2020

Record last verified: 2019-10

Locations

HU (4); FR (1)