Clinical trial NCT04654897: Mass Balance Study of [14C]-NT-814 Oral Suspension in Healthy Male Subjects
Official title: A Single Dose Study to Assess the Mass Balance Recovery, Absorption, Metabolism and Excretion of [14C]-NT-814 in Healthy Male Subjects After Oral Dosing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Bayer
Sponsor class: INDUSTRY
Collaborators: name: Quotient Sciences
First posted: 2020-12-04
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
Intervention model description: Open Label, single dose
Primary purpose: TREATMENT

Brief summary: This is a single centre, open-label, non-randomised study to assess the mass balance recovery, absorption, metabolism, and excretion of a single oral dose of \[14C\]-NT-814 in healthy male subjects. It is planned to enrol 6 subjects. Each subject will receive a single dose of 120 mg \[14C\] NT-814 containing not more than (NMT) 5.6 megabecquerel (MBq) \[14C\], administered as an oral suspension in the fasted state. Subjects will remain in the study until a mass balance cumulative recovery of \>90% and \<1% of the dose administered has been collected in urine and faeces within 2 separate, consecutive 24 hour periods.

Detailed description: Subjects will undergo preliminary screening procedures for the study up to 28 days before \[14C\]-NT-814 administration. Subjects will be admitted in the evening on the day prior to \[14C\]-NT-814 administration (Day -1) at which time further screening procedures will be undertaken to confirm eligibility. Subjects will be dosed in the morning of Day 1 following an overnight fast of a minimum of 8 hours.

It is planned that subjects will be released as a group when all subjects have achieved a mass balance cumulative recovery of \>90% and \<1% of the dose administered has been collected in urine and faeces within 2 separate, consecutive 24 hour periods.

This may result in the subjects being discharged as a group prior to completion of the planned residency period. If the mass balance discharge criteria are achieved during the planned residency period, collection of all samples (blood, urine, and faeces) will be stopped and subjects will undergo discharge assessments. If mass balance discharge criteria have not been met by all subjects by Day 15, the residency period for the subjects not achieving the mass balance discharge criteria may be extended up to a maximum of 48 hours (i.e., up to Day 17). Blood, urine and faeces will be collected for 24 hour intervals during the extended residency period whilst the subjects are resident in the clinic.

If the mass balance discharge criteria are still not met by Day 17, subjects will enter a home collection phase during which they will collect 24-hour urine and faeces on a daily basis up until Day 24 (or until the criteria are met) and then on a weekly basis starting on Day 31 (until criteria met or Day 45 reached). During the period of weekly collection, mass balance cumulative recovery will be estimated by means of interpolation.

No additional collections will be performed for subjects who still do not meet the criteria on Day 45. Subjects entering the home collection phase will return on Day 19 ± 12 hours for blood sample collection. Discharge safety assessments will be performed at the time of actual discharge from the clinical unit.

Eligibility criteria: Inclusion Criteria:

* Healthy males
* Aged 30 to 65 years inclusive at the time of signing informed consent.
* Body mass index (BMI) of 18.0 to 35.0 kg/m\^2, inclusive, as measured at screening.
* Must be able to understand the requirement of the study and be willing to participate in the whole study.
* Must have regular bowel movements (i.e., usual stool production of ≥1 and ≤3 stools per day).
* Must provide written informed consent.
* Must agree to adhere to the contraception requirements

Exclusion Criteria:

* Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1.
* Subjects who are, or are immediate family members of, a study site or Sponsor employee.
* Evidence of current SARS-CoV-2 infection.
* History of any drug or alcohol abuse in the past 2 years.
* Regular alcohol consumption \>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 \[7\], 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 biochemically verified Gilbert's Syndrome are allowed.
* Subjects with a presence of any of the following at screening, confirmed by a repeat test: AST, alanine aminotransferase or, gamma glutamyl transferase above the upper limit of normal.
* Confirmed positive drugs of abuse test result.
* Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) antibody results.
* Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of \<80 mL/min using the Cockcroft-Gault equation.
* History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or GI 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.
* Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood.
* Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies (other than up to 4 g of paracetamol per day) in the 14 days before IMP administration.
* History of GI surgery (with the exception of appendectomy unless it was performed within the previous 3 months).
* Acute diarrhoea or constipation in the 7 days before the predicted Day 1.
* 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: Day 45 (maximum)
measure: Mass Balance Recovery of Total Radioactivity: Cum%Ae(Urine)
timeFrame: Day 45 (maximum)
measure: Mass Balance Recovery of Total Radioactivity: CumAe(Faeces)
timeFrame: Day 45 (maximum)
measure: Mass Balance Recovery of Total Radioactivity: Cum%Ae(Faeces)
timeFrame: Day 45 (maximum)
measure: Mass Balance Recovery of Total Radioactivity: CumAe(Total)
timeFrame: Day 45 (maximum)
measure: Mass Balance Recovery of Total Radioactivity: Cum%Ae(Total)
timeFrame: Day 45 (maximum)
Secondary outcomes:
measure: AUC(0-tlast) of NT-814 (in plasma)
timeFrame: Day 45 (maximum)
measure: AUC(0-tlast) of Total Radioactivity (in plasma and whole blood)
timeFrame: Day 45 (maximum)
measure: Cmax of NT-814 (in plasma)
timeFrame: Day 45 (maximum)
measure: Cmax of Total Radioactivity (in plasma and whole blood)
timeFrame: Day 45 (maximum)
measure: Ae(urine) by interval
timeFrame: Day 45 (maximum)
measure: %Ae(urine) by interval
timeFrame: Day 45 (maximum)
measure: Ae(faeces) by interval
timeFrame: Day 45 (maximum)
measure: %Ae(faeces) by interval
timeFrame: Day 45 (maximum)
measure: Ae(total) by interval
timeFrame: Day 45 (maximum)
measure: %Ae(total) by interval
timeFrame: Day 45 (maximum)
measure: CumAe(urine) by interval
timeFrame: Day 45 (maximum)
measure: %CumAe(urine) by interval
timeFrame: Day 45 (maximum)
measure: CumAe(faeces) by interval
timeFrame: Day 45 (maximum)
measure: %CumAe(faeces) by interval
timeFrame: Day 45 (maximum)
measure: CumAe(total) by interval
timeFrame: Day 45 (maximum)
measure: %CumAe(total) by interval
timeFrame: Day 45 (maximum)
measure: Evaluation of the extent of distribution of Total Radioactivity (TR) into blood cells
timeFrame: Up to 45 days
measure: Number of subjects with treatment-emergent adverse events
timeFrame: Up to 45 days
measure: Laboratory Evaluations - number of subjects with clinically important changes in hematology and clinical chemistry parameters from baseline
timeFrame: Baseline, 24 hours post-baseline and at Discharge
measure: Vital Signs - number of subjects with clinically important changes in systolic and diastolic blood pressure and heart rate from baseline
timeFrame: Baseline, 1 hour, 4 hours, 24 hours post-baseline and at Discharge
measure: Number of subjects with clinically relevant findings in electrocardiogram (ECG) parameters from baseline
timeFrame: Baseline, 1 hour, 4 hours, 24 hours post-baseline and at Discharge
measure: Number of subjects with clinically significant abnormal findings in physical examination
timeFrame: Up to 45 days
Other outcomes:
Locations:
city: Ruddington
country: United Kingdom
facility: Quotient Sciences
state: Nottingham
Study officials:
affiliation: Quotient Sciences
name: Prinicipal Investigator
role: PRINCIPAL_INVESTIGATOR
References: