Mass Balance Study of NV-5138 in Healthy Male Subjects

Healthy Volunteers Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT05384977
• Other study ID #: NAV-17A-006
• Status: Completed
• Phase: Phase 1
• Start date: November 11, 2021
• Est. completion date: December 9, 2021

Study information

• Verified date: October 2021
• Source: Supernus Pharmaceuticals, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: December 9, 2021
• Est. primary completion date: December 9, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 40 Years to 65 Years

Eligibility

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.

Related Conditions & MeSH terms

• Healthy Volunteers

Intervention

Drug:
• [14C]-NV-5138
Single dose, given as oral solution, 1600 mg

Locations

Country	Name	City	State
United Kingdom	Quotient Sciences	Ruddington	Nottingham

Sponsors (1)

Lead Sponsor	Collaborator
Supernus Pharmaceuticals, Inc.

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	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
Secondary	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
Secondary	Cmax for NV-5138, metabolite M8 and total radioactivity in plasma whole blood	Maximum observed concentration	up to 168 hours post-dose
Secondary	Tmax for NV-5138, metabolite M8 and total radioactivity in plasma whole blood	Time of maximum observed concentration	up to 168 hours post-dose
Secondary	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
Secondary	t1/2 for NV-5138 and total radioactivity in plasma and whole blood	Terminal elimination half-life	up to 168 hours post-dose
Secondary	CL/F for NV-5138 in plasma	Total oral clearance	up to 168 hours post-dose
Secondary	Vz/F for NV-5138 in plasma	Apparent volume of distribution	up to 168 hours post-dose
Secondary	MPR Cmax in plasma	metabolite to parent ration based on Cmax	up to 168 hours post-dose
Secondary	MPR AUCinf in plasma	metabolite to parent ration based on AUCinf	up to 168 hours post-dose
Secondary	Whole blood to plasma partitioning for total radioactivity	The AUCinf ratio of whole blood to plasma	up to 168 hours post-dose
Secondary	CLR for NV-5138	Renal clearance	up to 168 hours post-dose
Secondary	Ae for total radioactivity in urine and feces	amount of total radioactivity excreted over each sampling period	up to 168 hours post-dose
Secondary	%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
Secondary	Characterization of metabolites in plasma, urine and fecal homogenates	Identification and quantification NV-5138 related metabolites	up to 168 hours post-dose