Healthy Volunteers
Conditions
Brief summary
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.
Interventions
DRUG[14C]-NV-5138
Single dose, given as oral solution, 1600 mg
Sponsors
Supernus Pharmaceuticals, Inc.
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
40 Years to 65 Years
Healthy volunteers
Yes
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative total radioactivity in urine and faeces | urine and fecal samples up to 168 hours post dose | The percentage of the radioactive dose recovered in urine, faeces and in total |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUCinf for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | up to 168 hours post-dose | Area under the concentration-time curve from time zero (pre-dose) to infinity |
| AUClast for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | up to 168 hours post-dose | Area under the concentration-time curve from time zero (pre-dose) to last time of quantifiable concentration |
| Cmax for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | up to 168 hours post-dose | Maximum observed concentration |
| Whole blood to plasma partitioning for total radioactivity | up to 168 hours post-dose | The AUCinf ratio of whole blood to plasma |
| Tmax for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | up to 168 hours post-dose | Time of maximum observed concentration |
| Tlast for NV-5138, metabolite M8 and total radioactivity in plasma whole blood | up to 168 hours post-dose | Time of the last measurable concentration |
| t1/2 for NV-5138 and total radioactivity in plasma and whole blood | up to 168 hours post-dose | Terminal elimination half-life |
| Ae for total radioactivity in urine and feces | up to 168 hours post-dose | amount of total radioactivity excreted over each sampling period |
| Vz/F for NV-5138 in plasma | up to 168 hours post-dose | Apparent volume of distribution |
| MPR Cmax in plasma | up to 168 hours post-dose | metabolite to parent ration based on Cmax |
| MPR AUCinf in plasma | up to 168 hours post-dose | metabolite to parent ration based on AUCinf |
| CLR for NV-5138 | up to 168 hours post-dose | Renal clearance |
| %Dose for total radioactivity in urine and feces | up to 168 hours post-dose | amount of total radioactivity eliminated in faeces expressed as a percentage of the radioactive dose administered over each sampling period |
| Characterization of metabolites in plasma, urine and fecal homogenates | up to 168 hours post-dose | Identification and quantification NV-5138 related metabolites |
| CL/F for NV-5138 in plasma | up to 168 hours post-dose | Total oral clearance |
Countries
United Kingdom
Outcome results
None listed