Clinical trial NCT03466567: A Trial Investigating the Effect of Probenecid and Ciclosporin on the Concentrations of SNAC in Healthy Subjects
Official title: A Trial Investigating the Effect of Probenecid and Ciclosporin on the Pharmacokinetics of SNAC in Healthy Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2018-03-15
Enrollment: 21
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: This is a 3-period cross-over study. The participants will be randomised to three treatment sequences each consisting of three treatment periods. One treatment period with a single dose of 3 mg oral semaglutide alone, one treatment period with a single dose of 600 mg ciclosporin 1 hour prior to administration of a single dose of 3 mg oral semaglutide and one treatment period with 500 mg probenecid administered twice daily for 3½ days with the last dose 2 hours prior to administration of a single dose of 3 mg oral semaglutide. Pharmacokinetics of sodium N-(8-(2-hydroxybenzoyl) amino) caprylate (SNAC) and SNAC metabolites will be assessed after each single dose of 3 mg oral semaglutide.
Primary purpose: TREATMENT

Brief summary: The aim of the study is to investigate the effect of the medicines, probenecid and ciclosporin on the concentrations of SNAC. SNAC is an ingredient of the semaglutide tablets. Participants will get 3 different treatments (that is 3 treatment periods): 1) a single dose of 3 mg semaglutide, 2) a single dose of 600 mg ciclosporin with 3 mg semaglutide, 3) 500 mg probenecid twice a day for 3 ½ days with a single dose of 3 mg semaglutide on the last day.

The sequence of treatments participants get is decided by chance. Probenecid and ciclosporin are available medicines. They are given by doctors. Semaglutide contains SNAC. It cannot be prescribed yet.

The study will last for up to 125 days. Participants will have 17 to 18 visits at the study centre. This includes short visits at the centre for blood sampling only. Participants will have several blood draws.


Eligibility criteria: Inclusion Criteria:

* Male or female of non-childbearing potential, aged 18-64 years (both inclusive) at the time of signing informed consent.
* Body mass index between 18.5 and 29.9 kg/sqm (both inclusive).
* Body weight greater than or equal to 50.0 kg.
* Considered to be generally healthy based on the medical history, physical examination, and the results of vital signs, electrocardiogram and clinical laboratory tests performed during the screening visit, as judged by the investigator.

Exclusion Criteria:

- Use of tobacco and nicotine products, defined as: A. Smoking more than 1 cigarette or the equivalent per day B. Not able or willing to refrain from smoking and use of nicotine substitute products during the in-house period(s).

* Presence of clinically significant gastrointestinal disorders or symptoms of gastrointestinal disorders potentially affecting absorption of drugs or nutrients, as judged by the investigator.
* History (as declared by the subject) of major surgical procedures involving the stomach potentially affecting absorption of trial products (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery).
* Known glucose-6-phosphate-dehydrogenase deficiency (as declared by the subject).

Primary outcomes:
measure: AUC0-tz,SNAC,SD, area under the SNAC plasma concentration-time curve from time 0 to time of the last quantifiable concentration after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: Cmax,SNAC,SD, maximum observed SNAC plasma concentration on the concentration-time curve after a single dose of oral semaglutide
timeFrame: 0-48 hours
Secondary outcomes:
measure: AUC0-tz,E494,SD, area under the SNAC metabolite E494 plasma concentration-time curve from time 0 to time of the last quantifiable concentration after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: Cmax,E494,SD, maximum observed SNAC metabolite E494 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: AUC0-tz,E506,SD, area under the SNAC metabolite E506 plasma concentration-time curve from time 0 to time of the last quantifiable concentration after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: Cmax,E506,SD, maximum observed SNAC metabolite E506 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: AUC0-∞,E1245,SD, area under the SNAC metabolite E1245 plasma concentration-time curve from time 0 to infinity after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: Cmax,E1245,SD, maximum observed SNAC metabolite E1245 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: AUC0-∞,E1246,SD, area under the SNAC metabolite E1246 plasma concentration-time curve from time 0 to infinity after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: Cmax,E1246,SD, maximum observed SNAC metabolite E1246 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: AUC0-∞,E1247,SD, area under the SNAC metabolite E1247 plasma concentration-time curve from time 0 to infinity after a single dose of oral semaglutide
timeFrame: 0-48 hours
measure: Cmax,E1247,SD, maximum observed SNAC metabolite E1247 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
timeFrame: 0-48 hours
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor and Disclosure (1452)
role: STUDY_DIRECTOR
References: