Mass Balance Study of NV-5138 in Healthy Male Subjects

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

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.

Study Overview

• Status: Completed
• Conditions: Healthy Volunteers
• Intervention / Treatment: Drug: [14C]-NV-5138

• Study Type: Interventional
• Enrollment (Actual): 6
• Phase: Phase 1

Contacts and Locations

Study Locations

• United Kingdom
  • Nottingham
    • Ruddington, Nottingham, United Kingdom, NG11 6JS
      • Quotient Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 40 years to 65 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

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

What is the study measuring?

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
Characterization of metabolites in plasma, urine and fecal homogenates	Identification and quantification NV-5138 related metabolites	up to 168 hours post-dose

Collaborators and Investigators

• Sponsor: Supernus Pharmaceuticals, Inc.

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2021
• Primary Completion (Actual): December 9, 2021
• Study Completion (Actual): December 9, 2021

Study Registration Dates

• First Submitted: May 12, 2022
• First Submitted That Met QC Criteria: May 17, 2022
• First Posted (Actual): May 23, 2022

Study Record Updates

• Last Update Posted (Actual): May 23, 2022
• Last Update Submitted That Met QC Criteria: May 17, 2022
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Other Study ID Numbers: NAV-17A-006

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No