Investigating the Influence of Oral Semaglutide on Pharmacokinetics of Metformin and Digoxin in Healthy Subjects

• Sponsor: Novo Nordisk A/S (Industry)
• Overall Status: Completed
• CT.gov ID: NCT02249910
• Collaborator: (none)
• Enrollment: 32
• Location: 1
• Arm: 1
• Actual Duration (Months): 5.6
• Patients Per Site Per Month: 5.8

Study Details

Study Description

Brief Summary

This trial is conducted in Europe. The aim of this trial is to investigate the influence of oral semaglutide on pharmacokinetics (the exposure of the trial drug in the body) of metformin and digoxin in healthy subjects.

Condition or Disease	Intervention/Treatment	Phase
Diabetes; Healthy	Drug: semaglutide; Drug: metformin; Drug: digoxin; Drug: placebo	Phase 1

Study Design

• Study Type: Interventional
• Actual Enrollment: 32 participants
• Allocation: Non-Randomized
• Intervention Model: Crossover Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Open-label, Single Arm, Sequential, Single Centre Trial Investigating the Influence of Oral Semaglutide on Pharmacokinetics of Metformin and Digoxin in Healthy Subjects
• Actual Study Start Date: Sep 18, 2014
• Actual Primary Completion Date: Mar 6, 2015
• Actual Study Completion Date: Mar 6, 2015

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Semaglutide

Drug: semaglutide; Oral administration of 5 mg daily for one week, then escalated to 10 mg daily for one week, followed by escalation to 20 mg daily for 41 days; Drug: metformin; Oral administration of 850 mg twice daily for 3 days followed by 850 mg on day 4, assessed in 3 dosing periods 1) alone, 2) co-administration with SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) and 3) co-administration with oral semaglutide.; Drug: digoxin; Oral administration of 0.5 mg single dose, assessed in 3 dosing periods 1) alone, 2) co-administration with SNAC (sodium N-[8-(2-hydroxybenzoyl) amino] caprylate) and 3) co-administration with oral semaglutide.; Drug: placebo; Oral administration of SNAC 300 mg. Will be administered with the morning dose of metformin (1st, 3rd, 5th and 7th dose). On Day 24, a single SNAC dose will be administered with digoxin.

Outcome Measures

Primary Outcome Measures

1. Area under the metformin plasma concentration-time curve [During a dosing interval (0 to12 hours) at steady state]

2. Area under the digoxin plasma concentration-time curve [From time 0 to infinity after single dose]

Secondary Outcome Measures

1. Maximum observed metformin plasma concentration [During a dosing interval (0 to 12 hours) at steady state]

2. Maximum observed digoxin plasma concentration [0 to 120 hours after single dose]

3. Maximum observed semaglutide plasma concentration [During a dosing interval (0 to 24 hours) at steady state]

4. Area under the SNAC plasma concentration-time curve [During a dosing interval (0 to 24 hours) at steady state]

5. Number of hypoglycaemic episodes [From the first dosing (Day 1) and until completion of the post treatment follow up visit (Day 118-122)]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Inclusion Criteria:

• Male or female, age 18-75 years (both inclusive) at the time of signing inform consent

• Body mass index (BMI) 20.0-29.9 kg/m^2 (both inclusive)

• A good general health based on medical history, physical examination, and results of vital signs, electrocardiogram and laboratory safety tests performed during the screening visit, as judged by the investigator

Exclusion Criteria:

• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using adequate contraceptive methods. Female of child bearing potential must use effective methods of birth control for the duration of the trial and for 5 weeks following last dose. Only highly effective methods of birth control are accepted (i.e., one that results in a less than 1% per year failure rate when used consistently and correctly, such as implants, injectables, combined oral contraceptives, and some intrauterine devices)

• History of Crohn's disease, ulcerative colitis, or other inflammatory bowel disease

• Hypertension (defined as sitting systolic blood pressure above 140 mmHg and/or diastolic blood pressure above 90 mmHg). If white-coat hypertension is suspected at the screening visit a repeated measurement is allowed

• Any blood draw in excess of 25 mL in the past month, or donation of blood or plasma in excess of 400 mL within the 3 months preceding screening

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: Global Clinical Registry (GCR, 1452), Novo Nordisk A/S

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Clinical Trials at Novo Nordisk

Publications

• Bækdal TA, Borregaard J, Hansen CW, Thomsen M, Anderson TW. Effect of Oral Semaglutide on the Pharmacokinetics of Lisinopril, Warfarin, Digoxin, and Metformin in Healthy Subjects. Clin Pharmacokinet. 2019 Sep;58(9):1193-1203. doi: 10.1007/s40262-019-00756-2.

• Responsible Party: Novo Nordisk A/S
• ClinicalTrials.gov Identifier: NCT02249910
• Other Study ID Numbers: NN9924-4145; 2013-004820-12; U1111-1150-0801
• First Posted: Sep 26, 2014
• Last Update Posted: Feb 17, 2020
• Last Verified: Feb 1, 2020

• Additional relevant MeSH terms: Metformin; Digoxin

Study Results

No Results Posted as of Feb 17, 2020