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

Primary Purpose

Diabetes, Diabetes Mellitus, Type 2

Status
Completed
Phase
Phase 1
Locations
Germany
Study Type
Interventional
Intervention
Semaglutide
Probenecid
Ciclosporin
Sponsored by
Novo Nordisk A/S
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Diabetes

Eligibility Criteria

18 Years - 64 Years (Adult)All SexesAccepts Healthy Volunteers

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).

Sites / Locations

  • Novo Nordisk Investigational Site

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Oral semaglutide, ciclosporin, probenecid

Probenecid, oral semaglutide, ciclosporin

Ciclosporin, probenecid, oral semaglutide

Arm Description

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

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

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

Outcomes

Primary Outcome Measures

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.
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.

Secondary Outcome Measures

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
Calculated based on plasma SNAC metabolite E494 activity measured in blood.
Cmax,E494,SD, maximum observed SNAC metabolite E494 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Calculated based on plasma SNAC metabolite E494 activity measured in blood.
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
Calculated based on plasma SNAC metabolite E506 activity measured in blood.
Cmax,E506,SD, maximum observed SNAC metabolite E506 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Calculated based on plasma SNAC metabolite E506 activity measured in blood.
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
Calculated based on plasma SNAC metabolite E1245 activity measured in blood.
Cmax,E1245,SD, maximum observed SNAC metabolite E1245 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Calculated based on plasma SNAC metabolite E1245 activity measured in blood.
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
Calculated based on plasma SNAC metabolite E1246 activity measured in blood.
Cmax,E1246,SD, maximum observed SNAC metabolite E1246 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Calculated based on plasma SNAC metabolite E1246 activity measured in blood.
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
Calculated based on plasma SNAC metabolite E1247 activity measured in blood.
Cmax,E1247,SD, maximum observed SNAC metabolite E1247 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Calculated based on plasma SNAC metabolite E1247 activity measured in blood.

Full Information

First Posted
March 9, 2018
Last Updated
June 18, 2019
Sponsor
Novo Nordisk A/S
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1. Study Identification

Unique Protocol Identification Number
NCT03466567
Brief Title
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

2. Study Status

Record Verification Date
June 2019
Overall Recruitment Status
Completed
Study Start Date
March 15, 2018 (Actual)
Primary Completion Date
July 10, 2018 (Actual)
Study Completion Date
July 10, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Novo Nordisk A/S

4. Oversight

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
Data Monitoring Committee
No

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Diabetes, Diabetes Mellitus, Type 2

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Crossover Assignment
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.
Masking
None (Open Label)
Allocation
Randomized
Enrollment
21 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Oral semaglutide, ciclosporin, probenecid
Arm Type
Experimental
Arm Description
Participants will receive oral semaglutide in treatment period 1, ciclosporin in treatment period 2, and probenecid in treatment period 3.
Arm Title
Probenecid, oral semaglutide, ciclosporin
Arm Type
Experimental
Arm Description
Participants will receive probenecid in treatment period 1, oral semaglutide in treatment period 2, and ciclosporin in treatment period 3.
Arm Title
Ciclosporin, probenecid, oral semaglutide
Arm Type
Experimental
Arm Description
Participants will receive ciclosporin in treatment period 1, probenecid in treatment period 2, and oral semaglutide in treatment period 3.
Intervention Type
Drug
Intervention Name(s)
Semaglutide
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Probenecid
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Ciclosporin
Intervention Description
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.
Primary Outcome Measure Information:
Title
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
Description
Calculated based on plasma SNAC activity measured in blood.
Time Frame
0-48 hours
Title
Cmax,SNAC,SD, maximum observed SNAC plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Description
Calculated based on plasma SNAC activity measured in blood.
Time Frame
0-48 hours
Secondary Outcome Measure Information:
Title
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
Description
Calculated based on plasma SNAC metabolite E494 activity measured in blood.
Time Frame
0-48 hours
Title
Cmax,E494,SD, maximum observed SNAC metabolite E494 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Description
Calculated based on plasma SNAC metabolite E494 activity measured in blood.
Time Frame
0-48 hours
Title
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
Description
Calculated based on plasma SNAC metabolite E506 activity measured in blood.
Time Frame
0-48 hours
Title
Cmax,E506,SD, maximum observed SNAC metabolite E506 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Description
Calculated based on plasma SNAC metabolite E506 activity measured in blood.
Time Frame
0-48 hours
Title
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
Description
Calculated based on plasma SNAC metabolite E1245 activity measured in blood.
Time Frame
0-48 hours
Title
Cmax,E1245,SD, maximum observed SNAC metabolite E1245 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Description
Calculated based on plasma SNAC metabolite E1245 activity measured in blood.
Time Frame
0-48 hours
Title
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
Description
Calculated based on plasma SNAC metabolite E1246 activity measured in blood.
Time Frame
0-48 hours
Title
Cmax,E1246,SD, maximum observed SNAC metabolite E1246 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Description
Calculated based on plasma SNAC metabolite E1246 activity measured in blood.
Time Frame
0-48 hours
Title
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
Description
Calculated based on plasma SNAC metabolite E1247 activity measured in blood.
Time Frame
0-48 hours
Title
Cmax,E1247,SD, maximum observed SNAC metabolite E1247 plasma concentration on the concentration-time curve after a single dose of oral semaglutide
Description
Calculated based on plasma SNAC metabolite E1247 activity measured in blood.
Time Frame
0-48 hours

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
64 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Clinical Reporting Anchor and Disclosure (1452)
Organizational Affiliation
Novo Nordisk A/S
Official's Role
Study Director
Facility Information:
Facility Name
Novo Nordisk Investigational Site
City
Berlin
ZIP/Postal Code
14050
Country
Germany

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
According to the Novo Nordisk disclosure commitment on novonordisk-trials.com.
IPD Sharing URL
http://www.novonordisk-trials.com/website/content/how-to-access-clinical-trial-datasets.aspx

Learn more about this trial

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

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