Mass Balance Study of NV-5138 in Healthy Male Subjects.

Study Overview
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Brief Summary
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The objective of this study is to assess the mass balance and routes of excretion of total radioactivity after a single oral dose of 1600 mg [14C]-NV-5138.

Official Title
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An Open-label, Single Dose, Mass Balance Study to Assess the Disposition of [14C]-NV-5138 in Healthy Male Subjects

Conditions
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Healthy Volunteers

Intervention / Treatment
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* Drug: [14C]-NV-5138


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy males aged 40 to 65 years inclusive at the time of signing informed consent. Body mass index of 18.0 to 32.0 kg/m2 as measured at screening 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 of >21 units per week and (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 shall participate in the study Subjects who have participated in an ADME study involving carbon-14 within 12 months of screening. Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator. Subjects with Gilbert's Syndrome are not allowed Clinically significant abnormalities on vital signs or ECGs as judged by the investigator at screening or pre-dose 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 gastrointestinal disease or neurological disorder, as judged by the investigator Any history of major depression disorder (MDD) requiring treatment or counselling or any other clinically significant psychiatric history, 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. Hay fever is allowed unless it is active 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 or 5 half-lives, whichever is longer, before IMP administration. COVID-19 vaccines are accepted concomitant medications. Exceptions may apply on a case by case basis, if considered not to interfere with the objectives of the study, as determined by the investigator. Subject answers yes to Suicidal Ideation Items 1 or 2 on the C-SSRS at screening Failure to satisfy the investigator of fitness to participate for any other reason.

Ages Eligible for Study
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Minimum Age: 40 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: [14C]-NV-5138<br>[14C]-NV-5138 oral solution | Drug: [14C]-NV-5138<br>* Single dose, given as oral solution, 1600 mg<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cumulative total radioactivity in urine and faeces | The percentage of the radioactive dose recovered in urine, faeces and in total | urine and fecal samples up to 168 hours post dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUCinf for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | Area under the concentration-time curve from time zero (pre-dose) to infinity | up to 168 hours post-dose | 
| AUClast for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration | up to 168 hours post-dose | 
| Cmax for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | Maximum observed concentration | up to 168 hours post-dose | 
| Tmax for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | Time of maximum observed concentration | up to 168 hours post-dose | 
| Tlast for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | Time of the last measurable concentration | up to 168 hours post-dose | 
| t1/2 for NV-5138 and total radioactivity in plasma and whole blood | Terminal elimination half-life | up to 168 hours post-dose | 
| CL/F for NV-5138 in plasma | Total oral clearance | up to 168 hours post-dose | 
| Vz/F for NV-5138 in plasma | Apparent volume of distribution | up to 168 hours post-dose | 
| MPR Cmax in plasma | metabolite to parent ration based on Cmax | up to 168 hours post-dose | 
| MPR AUCinf in plasma | metabolite to parent ration based on AUCinf | up to 168 hours post-dose | 
| Whole blood to plasma partitioning for total radioactivity | The AUCinf ratio of whole blood to plasma | up to 168 hours post-dose | 
| CLR for NV-5138 | Renal clearance | up to 168 hours post-dose | 
| Ae for total radioactivity in urine and feces | amount of total radioactivity excreted over each sampling period | up to 168 hours post-dose | 
| %Dose for total radioactivity in urine and feces | amount of total radioactivity eliminated in faeces expressed as a percentage of the radioactive dose administered over each sampling period | up to 168 hours post-dose or until mass balance criteria have been met | 
| Incidence of treatment-emergent adverse events | Incidence of adverse events | through study completion at one week |