Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-MD1003 in Healthy Male Subjects

Phase 1

Completed

Conditions: Healthy Volunteers

Interventions: Drug: [14C]-MD1003

Registration Number: NCT04223232

Lead Sponsor: MedDay Pharmaceuticals SA

Brief Summary: This single-center, open-label, non randomized Phase I study is being conducted to investigate the pharmacokinetics, mass balance and metabolite profiling and identification after a single oral dose of 100mg of \[14C\]-MD1003 in 6 healthy males subjects. The radioactivity will be followed in the blood, urine and faeces to study MD1003 metabolism.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: Male

Target Recruitment: 6

Inclusion Criteria

Healthy males
Age 30 to 65 years of age at the time of signing informed consent
Body mass index (BMI) of 18.0 to 30.0 kg/m2 as measured at screening
Must be willing and able to communicate and participate in the whole study
Must have regular bowel movements (ie average stool production of ≥1 and ≤3 stools per day)
Must provide written informed consent
Must agree to adhere to the contraception requirements of the protocol

Exclusion Criteria

Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1
Subjects who are study site employees, or immediate family members of a study site or sponsor employee
Subjects who have previously been enrolled in this study
History of any drug or alcohol abuse in the past 2 years
Regular alcohol consumption in males >21 units per week (1 unit = ½ pint beer, or a 25 mL shot of 40% spirit, 1.5 to 2 Units = 125 mL glass of wine, depending on type)
A confirmed positive alcohol breath test at screening or admission
Current smokers and those who have smoked within the last 12 months. A confirmed breath carbon monoxide reading of greater than 10 ppm at screening or admission
Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
Subjects with pregnant or lactating partners
Radiation exposure, including that from the present study, excluding background radiation but including diagnostic X-rays and other medical exposures, exceeding 5 mSv in the last 12 months or 10 mSv in the last 5 years. No occupationally exposed worker, as defined in the Ionising Radiation Regulations 2017, shall participate in the study
Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are allowed
Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in the protocol)
Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <80 mL/min using the Cockcroft-Gault equation
History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
Donation or loss of greater than 400 mL of blood within the previous 3 months
Subjects who are taking, or have taken, any prescribed or over-the-counter drug (other than 4 g of paracetamol per day), herbal remedies, vitamin B5 or dietary supplements containing lipoic acid in the 14 days before IMP administration. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the PI
Subjects who have had any intake of biotin (including as a nutritional supplement) in the 14 days before IMP administration
Failure to satisfy the investigator of fitness to participate for any other reason

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
MD1003	[14C]-MD1003	radiolabeled 14C MD1003 (High Dose Biotin) 100mg

Primary Outcome Measures

Name	Time	Method
Mass Balance Recovery of Total Radioactivity: CumAe (Urine)	Pre-dose to 312 hours post-dose	Cumulative amount of total radioactivity excreted in urine Measured at 0/12/24/48/72/96/120/144/168/192/216/240/264/288/312 hours
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Faeces)	Pre-dose to 312 hours post dose	Cumulative amount of total radioactivity excreted in faeces expressed as a percentage of the radioactive dose administered Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
Mass Balance Recovery of Total Radioactivity: CumAe(Total)	Pre-dose to 312 hours post dose	Cumulative amount of total radioactivity excreted in urine and faeces combined Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
Mass Balance Recovery of Total Radioactivity: CumAe (Faeces)	Pre-dose to 312 hours post-dose	Cumulative amount of total radioactivity excreted in faeces Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Total)	Pre-dose to 312 hours post dose	Cumulative amount of total radioactivity excreted in urine and faeces combined expressed as a percentage of the radioactive dose administered Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Urine)	Pre-dose to 312 hours post dose	Cumulative amount of total radioactivity excreted in urine expressed as a percentage of the radioactive dose administered Measured at 0/0.5/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168/192/216/240/264/288/312 hours.

Secondary Outcome Measures

Name	Time	Method
Time of Maximum Plasma Concentration (Tmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-last)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Elimination Half Life (t1/2) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Pre-dose to 168 hours	Measured at 0//1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Lambda-z for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Area Under Plasma Concentration Curve From 0 Time Extrapolated to Infinity (AUC(0-inf)) for MD1003 and Total Radioactivity	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-12)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
MPR AUC(0-inf) for Bisnorbiotin and Biotin Sulfoxide	Pre-dose to 168 hours	MPR = metabolite to parent ratio Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Number of Subjects With Adverse Events (AEs)	Overall period	2 months
Change From Baseline in Heart Rate in Beats Per Minute	Pre-dose to Day 10	Change from baseline measure (defined as Day 1, pre-dose). Measured at screening/Pre-dose/1/4/24/72/168 hours.
Maximum Plasma Concentration (Cmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Plasma Clearance (Vz/F) for MD1003	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Change From Baseline in Systolic Blood Pressure in mmHg	Pre-dose to Day 10	Change from baseline measure (defined as Day 1, pre-dose). Measured at screening/Pre-dose/1/4/24/72/168 hours.
Whole Blood: Plasma Concentration Ratios of Total Radioactivity	Pre-dose to 168 hours post-dose	Total radioactivity in whole blood versus total radioactivity in plasma concentration ratios at time intervals following a single oral administration of 100mg \[14C\]-MD1003 Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Change From Baseline in Diastolic Blood Pressure in mmHg	Pre-dose to Day 10	Change from baseline measure (defined as Day 1, pre-dose). Measured at screening/Pre-dose/1/4/24/72/168 hours.
Time Prior to the First Measurable Concentration (Tlag) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Percentage of AUC(0-extrap) Extrapolated Beyond the Last Measurable Concentration for MD1003 and Total Radioactivity	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Plasma Clearance (CL/F) for MD1003	Pre-dose to 168 hours	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
MPR Cmax for Bisnorbiotin and Biotin Sulfoxide	Pre-dose to 168 hours	MPR = metabolite to parent ratio Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.
Number of Subjects With Adverse Drug Reactions as Assessed by Investigator	Overall period
Change From Baseline in ECG (Electrocardiogram) QTcF Interval in Milliseconds	Pre-dose to Day 10	Change from baseline measure (defined as Day 1, pre-dose). Measured at screening/Pre-dose/1/4/24/72/168 hours.