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

An Open-Label, Single-Dose, Single-Period Study Designed to Assess the Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-MD1003 in Healthy Male Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [14C]-MD1003

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham, United Kingdom, NG11 6JS
    • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

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

Exclusion Criteria:

1. Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1
2. Subjects who are study site employees, or immediate family members of a study site or sponsor employee
3. Subjects who have previously been enrolled in this study
4. History of any drug or alcohol abuse in the past 2 years
5. 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)
6. A confirmed positive alcohol breath test at screening or admission
7. 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
8. Current users of e-cigarettes and nicotine replacement products and those who have used these products within the last 12 months
9. Subjects with pregnant or lactating partners
10. 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
11. Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening
12. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are allowed
13. Confirmed positive drugs of abuse test result (drugs of abuse tests are listed in the protocol)
14. Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) results
15. Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance of <80 mL/min using the Cockcroft-Gault equation
16. History of clinically significant cardiovascular, renal, hepatic, chronic respiratory or gastrointestinal disease, neurological or psychiatric disorder, as judged by the investigator
17. Serious adverse reaction or serious hypersensitivity to any drug or the formulation excipients
18. Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active
19. Donation or loss of greater than 400 mL of blood within the previous 3 months
20. 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
21. Subjects who have had any intake of biotin (including as a nutritional supplement) in the 14 days before IMP administration
22. Failure to satisfy the investigator of fitness to participate for any other reason

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: MD1003; radiolabeled 14C MD1003 (High Dose Biotin) 100mg	Drug: [14C]-MD1003; single oral dose of 100mg [14C]-MD1003

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mass Balance Recovery of Total Radioactivity: CumAe (Urine)	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	Pre-dose to 312 hours post-dose
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Urine)	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.	Pre-dose to 312 hours post dose
Mass Balance Recovery of Total Radioactivity: CumAe (Faeces)	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.	Pre-dose to 312 hours post-dose
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Faeces)	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.	Pre-dose to 312 hours post dose
Mass Balance Recovery of Total Radioactivity: CumAe(Total)	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.	Pre-dose to 312 hours post dose
Mass Balance Recovery of Total Radioactivity: Cum%Ae (Total)	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.	Pre-dose to 312 hours post dose

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Time Prior to the First Measurable Concentration (Tlag) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
Time of Maximum Plasma Concentration (Tmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
Maximum Plasma Concentration (Cmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 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	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
Area Under Plasma Concentration Curve From 0 Time Extrapolated to Infinity (AUC(0-inf)) for MD1003 and Total Radioactivity	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
Percentage of AUC(0-extrap) Extrapolated Beyond the Last Measurable Concentration for MD1003 and Total Radioactivity	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 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	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
Lambda-z for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
Plasma Clearance (CL/F) for MD1003	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
Plasma Clearance (Vz/F) for MD1003	Measured at 0/1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
Elimination Half Life (t1/2) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity	Measured at 0//1/1.5/2/3/4/6/8/12/18/24/36/48/72/96/120/144/168 hours.	Pre-dose to 168 hours
MPR Cmax for Bisnorbiotin and Biotin Sulfoxide	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.	Pre-dose to 168 hours
MPR AUC(0-inf) for Bisnorbiotin and Biotin Sulfoxide	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.	Pre-dose to 168 hours
Whole Blood: Plasma Concentration Ratios of Total Radioactivity	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.	Pre-dose to 168 hours post-dose
Number of Subjects With Adverse Events (AEs)	2 months	Overall period
Number of Subjects With Adverse Drug Reactions as Assessed by Investigator		Overall period
Change From Baseline in Systolic Blood Pressure in mmHg	Change from baseline measure (defined as Day 1, pre-dose). Measured at screening/Pre-dose/1/4/24/72/168 hours.	Pre-dose to Day 10
Change From Baseline in Diastolic Blood Pressure in mmHg	Change from baseline measure (defined as Day 1, pre-dose). Measured at screening/Pre-dose/1/4/24/72/168 hours.	Pre-dose to Day 10
Change From Baseline in Heart Rate in Beats Per Minute	Change from baseline measure (defined as Day 1, pre-dose). Measured at screening/Pre-dose/1/4/24/72/168 hours.	Pre-dose to Day 10
Change From Baseline in ECG (Electrocardiogram) QTcF Interval in Milliseconds	Change from baseline measure (defined as Day 1, pre-dose). Measured at screening/Pre-dose/1/4/24/72/168 hours.	Pre-dose to Day 10

Collaborators and Investigators

• Sponsor: MedDay Pharmaceuticals SA
• Collaborators: Quotient Sciences
• Investigators: Principal Investigator: Somasekhara Menakuru, MS, MRCS, Quotient Sciences Nottingham, UK, NG116JS

Study record dates

Study Major Dates

• Study Start (Actual): December 10, 2019
• Primary Completion (Actual): January 22, 2020
• Study Completion (Actual): January 22, 2020

Study Registration Dates

• First Submitted: December 13, 2019
• First Submitted That Met QC Criteria: January 7, 2020
• First Posted (Actual): January 10, 2020

Study Record Updates

• Last Update Posted (Actual): November 2, 2020
• Last Update Submitted That Met QC Criteria: October 29, 2020
• Last Verified: October 1, 2020

More Information

Terms related to this study

• Other Study ID Numbers: MD1003CT2019-03MB

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No