An open-label mass balance study of [14C]NST-6179 in healthy male subjects
- Conditions
- Intestinal failure associated liver disease (IFALD), also referred to as parenteral nutrition (PN) associated liver disease, and other potential indications.Digestive System
- Registration Number
- ISRCTN12367117
- Lead Sponsor
- orthSea Therapeutics B.V.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Ongoing
- Sex
- Male
- Target Recruitment
- 8
1.Must provide written informed consent.
2.Must be willing and able to communicate and participate in the whole study.
3.Aged 30 to 65 years inclusive at the time of signing informed consent.
4.Must agree to adhere to the contraception requirements defined in the protocol.
5.Healthy males according to the assessment of the investigator, as based on a complete medical history including a physical examination, vital signs, 12-lead ECG, and clinical laboratory tests without any clinically significant abnormalities.
6.Body mass index (BMI) of 18.0 to 32.0 kg/m², inclusive, as measured at screening.
7.Must have regular bowel movements (i.e. average stool production of =1 and =3 stools per day).
1.Serious adverse reaction or serious hypersensitivity to any drug or formulation excipients.
2.Presence or history of clinically significant allergy requiring treatment, as judged by the investigator. Hay fever is allowed unless it is active.
3.History of clinically significant cardiovascular, renal, hepatic, dermatological, chronic respiratory or GI disease, neurological or psychiatric disorder, as judged by the investigator.
4.Subjects who do not have suitable veins for multiple venepunctures/cannulation as assessed by the investigator or delegate at screening.
5.Clinically significant abnormal clinical chemistry, haematology or urinalysis as judged by the investigator (laboratory parameters are listed in the protocol). Subjects with Gilbert’s Syndrome are not allowed.
6.Positive hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCV Ab) or human immunodeficiency virus (HIV) 1 and 2 antibody results.
7.Evidence of renal impairment at screening, as indicated by an estimated creatinine clearance (CLcr) of <80 mL/min using the Cockcroft-Gault equation.
8.Subjects who have received any IMP in a clinical research study within the 90 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer.
9.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, shall participate in the study.
10.Subjects who have been administered IMP in an ADME study in the last 12 months.
11.Donation of blood or plasma within the previous 3 months or loss of greater than 400 mL of blood.
12.Subjects who are taking, or have taken, any prescribed or over-the-counter drug or herbal remedies, including topical medications, (other than up to 4 g of paracetamol per day in the 14 days prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer). Exceptions may apply, as determined by the investigator, if each of the following criteria are met: medication with a short half-life if the washout is such that no pharmacodynamic activity is expected by the time of dosing with IMP; and if the use of medication does not jeopardise the safety of the trial subject; and if the use of medication is not considered to interfere with the objectives of the study. COVID-19 vaccines are accepted concomitant medications.
13.Subjects who are using medications or products that are inhibitors or inducers of CYP2C9 or uridine 5'-diphospho-glucuronosyltransferase (UGT) in the 14 days (for CYP2C9/UGT inhibitors)/28 days (for CYP2C9/UGT inducers) prior to Day 1, or less than 5 elimination half-lives prior to Day 1, whichever is longer.
14.Use or intention to use any medications or products known to alter drug absorption, metabolism, or elimination processes, including St John’s Wort, in the 30 days prior to Day 1. Exceptions may apply, as determined by the investigator.
15.History of any drug or alcohol abuse in the past 2 years.
16.Regular alcohol consumption in males >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).
17.A confirmed positive alcohol breath test at screening or admission.
18.Current smokers and those who have smoked within the last 12 months.
19.Current us
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method 1. Mass balance recovery of total radioactivity in urine, faeces and all excreta of the test medicine from the body from samples taken from Day 1 up to a maximum of Day 10<br>2. Pharmacokinetics and total radioactivity of the test medicine in plasma and whole blood measured in blood samples taken from Day 1 up to a maximum of Day 10 <br>
- Secondary Outcome Measures
Name Time Method 1. Identify the metabolic profile (breakdown products) of the test medicine in plasma, urine and faeces in samples taken from Day 1 up to a maximum of Day 10.<br>2. Evaluation of whole blood:plasma concentration ratios for total radioactivity (to evaluate the extent of distribution of total radioactivity into blood cells), using samples taken between Day 1 up to a maximum of Day 10.<br>3. Adverse events (to assess tolerability of the test medicine) will be collected by asking volunteers how they are feeling, from the start of the trial until follow-up. Other safety measures (including vital signs, ECGs and laboratory safety tests) will also be assessed by standard phase I unit monitoring, at screening, from Day 1 to discharge from the ward.