HI Study to Assess and Compare the Pharmacokinetic Parameters of MD1003 in Hepatic Impaired Patients and Healthy Subjects

NCT04252417 | Terminated Phase 1

• 2 other identifiers: MD1003CT201901HI2019-002315-26
• Study Type: interventional
• Target: 15
• Locations: 2 countries
• Sites: 3

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 hepatic impaired patients and healthy subjects with normal hepatic function. The planned enrollment is 16 subjects (8 impaired patients and 8 healthy subjects).

Conditions

Healthy Volunteers; Hepatic Impairment of Moderate Child Pugh Category

Outcome Measures

Primary Outcomes (6)

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

  Blood samples will be collected

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

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

  Blood samples will be collected

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

• Observed maximum plasma concentration (Cmax) for MD1003

  Blood samples will be collected

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

• Measurement of concentration of MD1003

  Blood samples will be collected

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

• Measurement of concentration of Bisnorbiotin

  Blood samples will be collected

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

• Measurement of concentration of Biotin sulfoxide

  Blood samples will be collected

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

Secondary Outcomes (20)

• Measurement of plasma elimination half-life (t1/2) for MD1003

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

• Measurement of time to reach observed maximum plasma concentration (tmax) for MD1003

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

• Measurement of apparent volume of distribution (Vd/F) for MD1003

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

• Measurement of elimination rate constant (Kel) for MD1003

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

• Measurement of percentage of extrapolated AUCinf (%AUCextra) for MD1003

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

Study Arms (2)

Patients with hepatic impaired function

ACTIVE COMPARATOR

8 patients with hepatic impairment of moderate Child Pugh category

Drug: MD1003

Healthy subjects

ACTIVE COMPARATOR

Healthy volunteers will be matched with impaired hepatic function patients

Drug: MD1003

Interventions

MD1003 DRUG

Single oral dose administration of MD1003 at Day 1

Healthy subjects; Patients with hepatic 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 acceptable 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 acceptable effective non-hormonal method of contraception (bilateral tubal occlusion, vasectomized partner or intra-uterine device, sexual abstinence, male or female condom with spermicide);
• Negative serum pregnancy test at screening (if applicable);
• Normal renal function according to the age
• 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 hepatic impaired patients:
• Hepatic impairment of moderate Child Pugh category determined at screening (Class B: 7 to 9 points);
• Stable Hepatic dysfunction e.g. no clinical significant change in disease status within the last 30 days documented by recent medical history, including no worsening of clinical signs of hepatic impairment or no worsening of total Bilirubin or Prothrombin time\>50%.
• Stable treatment regimen or dose of medication
• Supine blood pressure ≤ 170/110 mmHg;

You may not qualify if:

• Subjects or Patients meeting any of the following criteria will not be included into the trial:
• 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);
• 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);
• 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;
• Subjects/Patients who are pregnant or breastfeeding. Subjects/Patients should not be enrolled if they plan to become pregnant during the time of study participation;
• Excessive consumption of beverages with xanthine bases (\> 4 cups or glasses / day);
• History or presence of drug abuse;
• 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 hematological, endocrine, pulmonary, gastrointestinal, cardiovascular, renal, 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;

Sponsors & Collaborators

• MedDay Pharmaceuticals SA: lead
• Eurofins Optimed: collaborator

Study Sites (3)

Eurofins Optimed

Gières, 38610, France

Location

DRC Drug Research Center Ltd.

Balatonfüred, 8231, Hungary

Location

Clinical Research Units Hungary Ltd.

Miskolc, 3528, Hungary

Location

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 11, 2019
• Primary Completion: March 17, 2020
• Study Completion: March 17, 2020
• Last Updated: May 13, 2020

Record last verified: 2020-01

Locations

HU (2); FR (1)