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

NCT02249910 | Completed Phase 1

• 3 other identifiers: NN9924-41452013-004820-12U1111-1150-0801
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

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.

Conditions

Diabetes; Healthy

Outcome Measures

Primary Outcomes (2)

• 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 Outcomes (5)

• 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)

Study Arms (1)

Semaglutide

EXPERIMENTAL

Drug: semaglutide; Drug: metformin; Drug: digoxin; Drug: placebo

Interventions

semaglutide DRUG

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

Semaglutide

metformin DRUG

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.

Semaglutide

digoxin DRUG

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.

Semaglutide

placebo DRUG

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.

Semaglutide

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (1)

Novo Nordisk Investigational Site

Berlin, 14050, Germany

Location

Related Publications (1)

• 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.

  PMID: 30945118 BACKGROUND

Related Links

• Clinical Trials at Novo Nordisk

MeSH Terms

Conditions

Diabetes Mellitus

Interventions

semaglutide; Metformin; Digoxin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Digitalis Glycosides; Cardenolides; Cardiac Glycosides; Cardanolides; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Glycosides; Carbohydrates

Study Officials

• Global Clinical Registry (GCR, 1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 23, 2014
• First Posted: September 26, 2014
• Study Start: September 18, 2014
• Primary Completion: March 6, 2015
• Study Completion: March 6, 2015
• Last Updated: February 17, 2020

Record last verified: 2020-02

Locations

DE (1)