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

Sponsor

Novo Nordisk A/S (Industry)

Overall Status

Completed

CT.gov ID

NCT03466567

Collaborator

(none)

Enrollment

Location

Arms

3.8

Actual Duration (Months)

5.5

Patients Per Site Per Month

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
Diabetes Diabetes Mellitus, Type 2	Drug: Semaglutide Drug: Probenecid Drug: Ciclosporin	Phase 1

Study Design

Study Type:

Interventional

Actual Enrollment :

21 participants

Allocation:

Randomized

Intervention Model:

Crossover Assignment

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.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)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Mar 15, 2018

Actual Primary Completion Date :

Jul 10, 2018

Actual Study Completion Date :

Jul 10, 2018

Arms and Interventions

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.	Drug: Semaglutide 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. Drug: Probenecid 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. Drug: Ciclosporin 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.	Drug: Semaglutide 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. Drug: Probenecid 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. Drug: Ciclosporin 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.	Drug: Semaglutide 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. Drug: Probenecid 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. Drug: Ciclosporin 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.

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.

Drug: Semaglutide

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.

Drug: Probenecid

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.

Drug: Ciclosporin

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.

Drug: Semaglutide

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.

Drug: Probenecid

Drug: Ciclosporin

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.

Drug: Semaglutide

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.

Drug: Probenecid

Drug: Ciclosporin

Outcome Measures

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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
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 [0-48 hours]
Calculated based on plasma SNAC metabolite E1247 activity measured in blood.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 64 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

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).

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Novo Nordisk Investigational Site	Berlin		Germany	14050

Sponsors and Collaborators

Novo Nordisk A/S

Investigators

Study Director: Clinical Reporting Anchor and Disclosure (1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

Responsible Party:

Novo Nordisk A/S

ClinicalTrials.gov Identifier:

NCT03466567

Other Study ID Numbers:

NN9924-4394
U1111-1197-9088
2017-002498-21

First Posted:

Mar 15, 2018

Last Update Posted:

Jun 19, 2019

Last Verified:

Jun 1, 2019

Individual Participant Data (IPD) Sharing Statement:

Yes

Plan to Share IPD:

Yes

Studies a U.S. FDA-regulated Drug Product:

Yes

Studies a U.S. FDA-regulated Device Product:

Product Manufactured in and Exported from the U.S.:

Yes

Additional relevant MeSH terms:

Diabetes Mellitus

Diabetes Mellitus, Type 2

Cyclosporine

Probenecid

Cyclosporins

Study Results

No Results Posted as of Jun 19, 2019