A Trial Investigating the Effect of Probenecid and Ciclosporin on the Concentrations of SNAC in Healthy Subjects

NCT03466567 | Completed Phase 1 FDA Drug

• 3 other identifiers: NN9924-4394U1111-1197-90882017-002498-21
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes; Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (2)

• 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

  Calculated based on plasma SNAC activity measured in blood.

  0-48 hours

• Cmax,SNAC,SD, maximum observed SNAC plasma concentration on the concentration-time curve after a single dose of oral semaglutide

  Calculated based on plasma SNAC activity measured in blood.

  0-48 hours

Secondary Outcomes (10)

• 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

  0-48 hours

• Cmax,E494,SD, maximum observed SNAC metabolite E494 plasma concentration on the concentration-time curve after a single dose of oral semaglutide

  0-48 hours

• 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

  0-48 hours

• Cmax,E506,SD, maximum observed SNAC metabolite E506 plasma concentration on the concentration-time curve after a single dose of oral semaglutide

  0-48 hours

• 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

  0-48 hours

Study Arms (3)

Oral semaglutide, ciclosporin, probenecid

EXPERIMENTAL

Participants will receive oral semaglutide in treatment period 1, ciclosporin in treatment period 2, and probenecid in treatment period 3.

Drug: Semaglutide; Drug: Probenecid; Drug: Ciclosporin

Probenecid, oral semaglutide, ciclosporin

EXPERIMENTAL

Participants will receive probenecid in treatment period 1, oral semaglutide in treatment period 2, and ciclosporin in treatment period 3.

Drug: Semaglutide; Drug: Probenecid; Drug: Ciclosporin

Ciclosporin, probenecid, oral semaglutide

EXPERIMENTAL

Participants will receive ciclosporin in treatment period 1, probenecid in treatment period 2, and oral semaglutide in treatment period 3.

Drug: Semaglutide; Drug: Probenecid; Drug: Ciclosporin

Interventions

Semaglutide DRUG

A single dose of 3 mg semaglutide tablet alone will be administered orally. Trial product administration will take place in the morning after overnight fasting for at least 6 hours.

Ciclosporin, probenecid, oral semaglutide; Oral semaglutide, ciclosporin, probenecid; Probenecid, oral semaglutide, ciclosporin

Probenecid DRUG

A dose of 500 mg probenecid (2 tablets of 250 mg) will be administered orally twice daily for 3½ days (7 trial product administrations in total). On the 4th day, the last probenecid administration will take place 2 hours prior to administration of a single dose of 3 mg oral semaglutide tablet. The last trial product administrations will take place in the morning after overnight fasting for at least 6 hours.

Ciclosporin, probenecid, oral semaglutide; Oral semaglutide, ciclosporin, probenecid; Probenecid, oral semaglutide, ciclosporin

Ciclosporin DRUG

A single dose of 600 mg ciclosporin (6 capsules of 100 mg) will be administered orally 1 hour prior to administration of a single dose of 3 mg oral semaglutide tablet. Trial product administration will take place in the morning after overnight fasting for at least 6 hours.

Ciclosporin, probenecid, oral semaglutide; Oral semaglutide, ciclosporin, probenecid; Probenecid, oral semaglutide, ciclosporin

Eligibility Criteria

• Age: 18 Years - 64 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• \- 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).

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (1)

Novo Nordisk Investigational Site

Berlin, 14050, Germany

Location

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 2

Interventions

semaglutide; Probenecid; Cyclosporine

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Sulfonamides; Amides; Organic Chemicals; Sulfones; Sulfur Compounds; Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Clinical Reporting Anchor and Disclosure (1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: 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.

Study Record Dates

• First Submitted: March 9, 2018
• First Posted: March 15, 2018
• Study Start: March 15, 2018
• Primary Completion: July 10, 2018
• Study Completion: July 10, 2018
• Last Updated: June 19, 2019

Record last verified: 2019-06

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)