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

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04223232
• Other study ID #: MD1003CT2019-03MB
• Status: Completed
• Phase: Phase 1
• Start date: December 10, 2019
• Est. completion date: January 22, 2020

Study information

• Verified date: October 2020
• Source: MedDay Pharmaceuticals SA
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: January 22, 2020
• Est. primary completion date: January 22, 2020
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 30 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• [14C]-MD1003
single oral dose of 100mg [14C]-MD1003

Locations

Country	Name	City	State
United Kingdom	Quotient Sciences	Nottingham

Sponsors (2)

Lead Sponsor	Collaborator
MedDay Pharmaceuticals SA	Quotient Sciences

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	Number of Subjects With Adverse Events (AEs)	2 months	Overall period
Secondary	Number of Subjects With Adverse Drug Reactions as Assessed by Investigator		Overall period
Secondary	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
Secondary	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
Secondary	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
Secondary	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