Clinical trial NCT04223232: Mass Balance Recovery, Metabolite Profile and Metabolite Identification of [14C]-MD1003 in Healthy Male Subjects
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: MedDay Pharmaceuticals SA
Sponsor class: INDUSTRY
Collaborators: name: Quotient Sciences
First posted: 2020-01-10
Enrollment: 6
Sex: MALE
Minimum age (years): 30
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: HEALTH_SERVICES_RESEARCH

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.


Eligibility criteria: 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

Primary outcomes:
measure: Mass Balance Recovery of Total Radioactivity: CumAe (Urine)
timeFrame: Pre-dose to 312 hours post-dose
measure: Mass Balance Recovery of Total Radioactivity: Cum%Ae (Urine)
timeFrame: Pre-dose to 312 hours post dose
measure: Mass Balance Recovery of Total Radioactivity: CumAe (Faeces)
timeFrame: Pre-dose to 312 hours post-dose
measure: Mass Balance Recovery of Total Radioactivity: Cum%Ae (Faeces)
timeFrame: Pre-dose to 312 hours post dose
measure: Mass Balance Recovery of Total Radioactivity: CumAe(Total)
timeFrame: Pre-dose to 312 hours post dose
measure: Mass Balance Recovery of Total Radioactivity: Cum%Ae (Total)
timeFrame: Pre-dose to 312 hours post dose
Secondary outcomes:
measure: Time Prior to the First Measurable Concentration (Tlag) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: Time of Maximum Plasma Concentration (Tmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: Maximum Plasma Concentration (Cmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-last)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: Area Under Plasma Concentration Curve From 0 Time Extrapolated to Infinity (AUC(0-inf)) for MD1003 and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: Percentage of AUC(0-extrap) Extrapolated Beyond the Last Measurable Concentration for MD1003 and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-12)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: Lambda-z for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: Plasma Clearance (CL/F) for MD1003
timeFrame: Pre-dose to 168 hours
measure: Plasma Clearance (Vz/F) for MD1003
timeFrame: Pre-dose to 168 hours
measure: Elimination Half Life (t1/2) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity
timeFrame: Pre-dose to 168 hours
measure: MPR Cmax for Bisnorbiotin and Biotin Sulfoxide
timeFrame: Pre-dose to 168 hours
measure: MPR AUC(0-inf) for Bisnorbiotin and Biotin Sulfoxide
timeFrame: Pre-dose to 168 hours
measure: Whole Blood: Plasma Concentration Ratios of Total Radioactivity
timeFrame: Pre-dose to 168 hours post-dose
measure: Number of Subjects With Adverse Events (AEs)
timeFrame: Overall period
measure: Number of Subjects With Adverse Drug Reactions as Assessed by Investigator
timeFrame: Overall period
measure: Change From Baseline in Systolic Blood Pressure in mmHg
timeFrame: Pre-dose to Day 10
measure: Change From Baseline in Diastolic Blood Pressure in mmHg
timeFrame: Pre-dose to Day 10
measure: Change From Baseline in Heart Rate in Beats Per Minute
timeFrame: Pre-dose to Day 10
measure: Change From Baseline in ECG (Electrocardiogram) QTcF Interval in Milliseconds
timeFrame: Pre-dose to Day 10
Other outcomes:
Locations:
city: Nottingham
country: United Kingdom
facility: Quotient Sciences
Study officials:
affiliation: Quotient Sciences Nottingham, UK, NG116JS
name: Somasekhara Menakuru, MS, MRCS
role: PRINCIPAL_INVESTIGATOR
References: