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

An Open-label, Single Arm, Sequential, Single Centre Trial Investigating the Influence of Oral Semaglutide on Pharmacokinetics of Metformin and Digoxin in Healthy Subjects

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.

Study Overview

• Status: Completed
• Conditions: Healthy; Diabetes
• Intervention / Treatment: Drug: semaglutide; Drug: metformin; Drug: digoxin; Drug: placebo

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 14050
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Area under the metformin plasma concentration-time curve	During a dosing interval (0 to12 hours) at steady state
Area under the digoxin plasma concentration-time curve	From time 0 to infinity after single dose

Secondary Outcome Measures

Outcome Measure	Time Frame
Maximum observed metformin plasma concentration	During a dosing interval (0 to 12 hours) at steady state
Maximum observed digoxin plasma concentration	0 to 120 hours after single dose
Maximum observed semaglutide plasma concentration	During a dosing interval (0 to 24 hours) at steady state
Area under the SNAC plasma concentration-time curve	During a dosing interval (0 to 24 hours) at steady state
Number of hypoglycaemic episodes	From the first dosing (Day 1) and until completion of the post treatment follow up visit (Day 118-122)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Publications and helpful links

General Publications

• Baekdal 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.

Helpful Links

• Clinical Trials at Novo Nordisk

Study record dates

Study Major Dates

• Study Start (Actual): September 18, 2014
• Primary Completion (Actual): March 6, 2015
• Study Completion (Actual): March 6, 2015

Study Registration Dates

• First Submitted: September 23, 2014
• First Submitted That Met QC Criteria: September 23, 2014
• First Posted (Estimate): September 26, 2014

Study Record Updates

• Last Update Posted (Actual): February 17, 2020
• Last Update Submitted That Met QC Criteria: February 13, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Hypoglycemic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Enzyme Inhibitors; Protective Agents; Cardiotonic Agents; Digoxin; Metformin
• Other Study ID Numbers: NN9924-4145; 2013-004820-12 (EudraCT Number); U1111-1150-0801 (Other Identifier: WHO)