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

June 18, 2019 updated by: Novo Nordisk A/S

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

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.

Study Overview

Study Type

Interventional

Enrollment (Actual)

21

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

      • Berlin, Germany, 14050
        • Novo Nordisk INvestigational Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

16 years to 62 years (Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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).

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oral semaglutide, ciclosporin, probenecid
Participants will receive oral semaglutide in treatment period 1, ciclosporin in treatment period 2, and probenecid in treatment period 3.
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.
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.
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.
Experimental: Probenecid, oral semaglutide, ciclosporin
Participants will receive probenecid in treatment period 1, oral semaglutide in treatment period 2, and ciclosporin in treatment period 3.
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.
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.
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.
Experimental: Ciclosporin, probenecid, oral semaglutide
Participants will receive ciclosporin in treatment period 1, probenecid in treatment period 2, and oral semaglutide in treatment period 3.
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.
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.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 0-48 hours
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
Time Frame: 0-48 hours
Calculated based on plasma SNAC activity measured in blood.
0-48 hours

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E494 activity measured in blood.
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
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E494 activity measured in blood.
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
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E506 activity measured in blood.
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
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E506 activity measured in blood.
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
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E1245 activity measured in blood.
0-48 hours
Cmax,E1245,SD, maximum observed SNAC metabolite E1245 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E1245 activity measured in blood.
0-48 hours
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
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E1246 activity measured in blood.
0-48 hours
Cmax,E1246,SD, maximum observed SNAC metabolite E1246 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E1246 activity measured in blood.
0-48 hours
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
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E1247 activity measured in blood.
0-48 hours
Cmax,E1247,SD, maximum observed SNAC metabolite E1247 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Time Frame: 0-48 hours
Calculated based on plasma SNAC metabolite E1247 activity measured in blood.
0-48 hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

March 15, 2018

Primary Completion (Actual)

July 10, 2018

Study Completion (Actual)

July 10, 2018

Study Registration Dates

First Submitted

March 9, 2018

First Submitted That Met QC Criteria

March 9, 2018

First Posted (Actual)

March 15, 2018

Study Record Updates

Last Update Posted (Actual)

June 19, 2019

Last Update Submitted That Met QC Criteria

June 18, 2019

Last Verified

June 1, 2019

More Information

Terms related to this study

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Yes

IPD Plan Description

According to the Novo Nordisk disclosure commitment on novonordisk-trials.com.

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

Yes

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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