Healthy Volunteers
Conditions
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.
Interventions
DRUG[14C]-MD1003
single oral dose of 100mg \[14C\]-MD1003
Sponsors
Quotient Sciences
MedDay Pharmaceuticals SA
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
30 Years to 65 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 (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. |
| 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 (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: 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| Number of Subjects With Adverse Events (AEs) | Overall period | 2 months |
| Number of Subjects With Adverse Drug Reactions as Assessed by Investigator | Overall period | — |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
| 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. |
Countries
United Kingdom
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| MD1003 radiolabeled 14C MD1003 (High Dose Biotin) 100mg
\[14C\]-MD1003: single oral dose of 100mg \[14C\]-MD1003 | 6 |
| Total | 6 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Withdrawal by Subject | 1 |
Baseline characteristics
| Characteristic | MD1003 |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants |
| Age, Continuous | 43.3 years STANDARD_DEVIATION 12 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 6 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants |
| Race (NIH/OMB) More than one race | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 4 Participants |
| Region of Enrollment United Kingdom | 6 participants |
| Sex: Female, Male Female | 0 Participants |
| Sex: Female, Male Male | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 6 |
| other Total, other adverse events | 2 / 6 |
| serious Total, serious adverse events | 0 / 6 |
Outcome results
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.
Time frame: Pre-dose to 312 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MD1003 | Mass Balance Recovery of Total Radioactivity: Cum%Ae (Faeces) | 16.009 percentage | Standard Deviation 8.617 |
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.
Time frame: Pre-dose to 312 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MD1003 | Mass Balance Recovery of Total Radioactivity: CumAe (Faeces) | 16.0 mg equiv | Standard Deviation 8.63 |
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.
Time frame: Pre-dose to 312 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MD1003 | Mass Balance Recovery of Total Radioactivity: Cum%Ae (Total) | 86.795 percentage | Standard Deviation 9.235 |
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.
Time frame: Pre-dose to 312 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MD1003 | Mass Balance Recovery of Total Radioactivity: CumAe(Total) | 86.9 mg equiv | Standard Deviation 9.25 |
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.
Time frame: Pre-dose to 312 hours post dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MD1003 | Mass Balance Recovery of Total Radioactivity: Cum%Ae (Urine) | 70.786 percentage | Standard Deviation 16.874 |
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
Time frame: Pre-dose to 312 hours post-dose
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| MD1003 | Mass Balance Recovery of Total Radioactivity: CumAe (Urine) | 70.9 mg equiv | Standard Deviation 16.9 |
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.
Time frame: Pre-dose to 168 hours
Population: For total radioactivity: for 3 patients, extrapolated portion of AUC(0-inf) \>20%.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | Area Under Plasma Concentration Curve From 0 Time Extrapolated to Infinity (AUC(0-inf)) for MD1003 and Total Radioactivity | MD1003 | 3650 ng.h/mL |
| MD1003 | Area Under Plasma Concentration Curve From 0 Time Extrapolated to Infinity (AUC(0-inf)) for MD1003 and Total Radioactivity | Total radioactivity | 2850 ng.h/mL |
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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MD1003 | Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-12)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | MD1003 | 1760 ng.h/mL | Geometric Coefficient of Variation 16.5 |
| MD1003 | Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-12)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Bisnorbiotin | 279 ng.h/mL | Geometric Coefficient of Variation 26.4 |
| MD1003 | Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-12)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Biotin Sulfoxide | 90.1 ng.h/mL | Geometric Coefficient of Variation 23.7 |
| MD1003 | Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-12)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Total radioactivity | 2680 ng.h/mL | Geometric Coefficient of Variation 10.6 |
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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-last)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | MD1003 | 3350 ng.h/mL |
| MD1003 | Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-last)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Bisnorbiotin | 514 ng.h/mL |
| MD1003 | Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-last)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Biotin Sulfoxide | 74.3 ng.h/mL |
| MD1003 | Area Under Plasma Concentration Curve From 0 Time to Last Measurable Concentration (AUC(0-last)) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Total radioactivity | 2690 ng.h/mL |
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.
Time frame: Pre-dose to Day 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MD1003 | Change From Baseline in Diastolic Blood Pressure in mmHg | 1H | 3.2 mmHg | Standard Deviation 5.9 |
| MD1003 | Change From Baseline in Diastolic Blood Pressure in mmHg | 4H | 2.5 mmHg | Standard Deviation 6.1 |
| MD1003 | Change From Baseline in Diastolic Blood Pressure in mmHg | 24H | 2.0 mmHg | Standard Deviation 6.6 |
| MD1003 | Change From Baseline in Diastolic Blood Pressure in mmHg | 72H | -0.5 mmHg | Standard Deviation 5.8 |
| MD1003 | Change From Baseline in Diastolic Blood Pressure in mmHg | Discharge | 4.7 mmHg | Standard Deviation 6.9 |
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.
Time frame: Pre-dose to Day 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MD1003 | Change From Baseline in ECG (Electrocardiogram) QTcF Interval in Milliseconds | 1H | 2.2 msec | Standard Deviation 6.9 |
| MD1003 | Change From Baseline in ECG (Electrocardiogram) QTcF Interval in Milliseconds | 4H | 2.7 msec | Standard Deviation 3.9 |
| MD1003 | Change From Baseline in ECG (Electrocardiogram) QTcF Interval in Milliseconds | 24H | 1.0 msec | Standard Deviation 4.6 |
| MD1003 | Change From Baseline in ECG (Electrocardiogram) QTcF Interval in Milliseconds | Discharge | 1.0 msec | Standard Deviation 11.5 |
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.
Time frame: Pre-dose to Day 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MD1003 | Change From Baseline in Heart Rate in Beats Per Minute | 1H | -3.7 bpm | Standard Deviation 3 |
| MD1003 | Change From Baseline in Heart Rate in Beats Per Minute | 4H | -4.0 bpm | Standard Deviation 4.8 |
| MD1003 | Change From Baseline in Heart Rate in Beats Per Minute | 24H | -2.5 bpm | Standard Deviation 5.5 |
| MD1003 | Change From Baseline in Heart Rate in Beats Per Minute | 72H | -2.0 bpm | Standard Deviation 6 |
| MD1003 | Change From Baseline in Heart Rate in Beats Per Minute | Discharge | 3.3 bpm | Standard Deviation 9.9 |
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.
Time frame: Pre-dose to Day 10
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| MD1003 | Change From Baseline in Systolic Blood Pressure in mmHg | 1H | 0.7 mmHg | Standard Deviation 4.9 |
| MD1003 | Change From Baseline in Systolic Blood Pressure in mmHg | 4H | -3.5 mmHg | Standard Deviation 8 |
| MD1003 | Change From Baseline in Systolic Blood Pressure in mmHg | 24H | -1.0 mmHg | Standard Deviation 10.3 |
| MD1003 | Change From Baseline in Systolic Blood Pressure in mmHg | 72H | -2.8 mmHg | Standard Deviation 11.4 |
| MD1003 | Change From Baseline in Systolic Blood Pressure in mmHg | Discharge | 0.5 mmHg | Standard Deviation 6.9 |
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.
Time frame: Pre-dose to 168 hours
Population: For Bisnorbiotin: terminal slopes could not be reliably determined for all, due to an unacceptable coefficient of determination (ie, R2 \< 0.9).~For Biotin sulfoxide: terminal slopes could not be reliably determined all, due to an unacceptable coefficient of determination (ie, R2 \< 0.9) or insufficient data points after Cmax.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | Elimination Half Life (t1/2) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | MD1003 | 30.625 hours |
| MD1003 | Elimination Half Life (t1/2) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Bisnorbiotin | 33.176 hours |
| MD1003 | Elimination Half Life (t1/2) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Biotin Sulfoxide | 10.010 hours |
| MD1003 | Elimination Half Life (t1/2) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Total radioactivity | 4.502 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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | Lambda-z for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | MD1003 | 0.02302 1/Hours |
| MD1003 | Lambda-z for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Bisnorbiotin | 0.02251 1/Hours |
| MD1003 | Lambda-z for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Biotin Sulfoxide | 0.11829 1/Hours |
| MD1003 | Lambda-z for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Total radioactivity | 0.20071 1/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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | Maximum Plasma Concentration (Cmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | MD1003 | 387 ng/mL |
| MD1003 | Maximum Plasma Concentration (Cmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Bisnorbiotin | 45.5 ng/mL |
| MD1003 | Maximum Plasma Concentration (Cmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Biotin Sulfoxide | 14.5 ng/mL |
| MD1003 | Maximum Plasma Concentration (Cmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Total radioactivity | 501 ng/mL |
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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | MPR AUC(0-inf) for Bisnorbiotin and Biotin Sulfoxide | Bisnorbiotin | 0.1731 none (ratio) |
| MD1003 | MPR AUC(0-inf) for Bisnorbiotin and Biotin Sulfoxide | Biotin sulfoxide | 0.0204 none (ratio) |
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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | MPR Cmax for Bisnorbiotin and Biotin Sulfoxide | Bisnorbiotin | 0.1327 none (ratio) |
| MD1003 | MPR Cmax for Bisnorbiotin and Biotin Sulfoxide | Biotin Sulfoxide | 0.0349 none (ratio) |
Secondary
Number of Subjects With Adverse Drug Reactions as Assessed by Investigator
Time frame: Overall period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MD1003 | Number of Subjects With Adverse Drug Reactions as Assessed by Investigator | 0 Participants |
Secondary
Number of Subjects With Adverse Events (AEs)
2 months
Time frame: Overall period
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| MD1003 | Number of Subjects With Adverse Events (AEs) | 2 Participants |
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.
Time frame: Pre-dose to 168 hours
Population: For total radioactivity: for 3 patients, extrapolated portion of AUC(0-inf) \>20%.
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | Percentage of AUC(0-extrap) Extrapolated Beyond the Last Measurable Concentration for MD1003 and Total Radioactivity | MD1003 | 8.405 percentage of AUC(0-extrap) |
| MD1003 | Percentage of AUC(0-extrap) Extrapolated Beyond the Last Measurable Concentration for MD1003 and Total Radioactivity | Total radioactivity | 15.171 percentage of AUC(0-extrap) |
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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MD1003 | Plasma Clearance (CL/F) for MD1003 | 465 mL/min |
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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Value (MEAN) |
|---|---|---|
| MD1003 | Plasma Clearance (Vz/F) for MD1003 | 1230 L |
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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | Time of Maximum Plasma Concentration (Tmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | MD1003 | 2.086 hours |
| MD1003 | Time of Maximum Plasma Concentration (Tmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Bisnorbiotin | 4.011 hours |
| MD1003 | Time of Maximum Plasma Concentration (Tmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Biotin Sulfoxide | 2.667 hours |
| MD1003 | Time of Maximum Plasma Concentration (Tmax) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Total radioactivity | 2.667 hours |
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.
Time frame: Pre-dose to 168 hours
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| MD1003 | Time Prior to the First Measurable Concentration (Tlag) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | MD1003 | 0.083 hours |
| MD1003 | Time Prior to the First Measurable Concentration (Tlag) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Bisnorbiotin | 0.753 hours |
| MD1003 | Time Prior to the First Measurable Concentration (Tlag) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Biotin Sulfoxide | 0.753 hours |
| MD1003 | Time Prior to the First Measurable Concentration (Tlag) for MD1003, Bisnorbiotin, Biotin Sulfoxide and Total Radioactivity | Total radioactivity | 0.000 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.
Time frame: Pre-dose to 168 hours post-dose
| Arm | Measure | Group | Value (GEOMETRIC_MEAN) | Dispersion |
|---|---|---|---|---|
| MD1003 | Whole Blood: Plasma Concentration Ratios of Total Radioactivity | 1 H | 1.298 % radioactivity whole blood/plasma | Geometric Coefficient of Variation 5 |
| MD1003 | Whole Blood: Plasma Concentration Ratios of Total Radioactivity | 4 H | 0.931 % radioactivity whole blood/plasma | Geometric Coefficient of Variation 14.6 |
| MD1003 | Whole Blood: Plasma Concentration Ratios of Total Radioactivity | 8 H | 1.365 % radioactivity whole blood/plasma | Geometric Coefficient of Variation 7 |
| MD1003 | Whole Blood: Plasma Concentration Ratios of Total Radioactivity | 12 H | 1.708 % radioactivity whole blood/plasma | Geometric Coefficient of Variation 9.3 |