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

Healthy Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02249910
• Other study ID #: NN9924-4145
• Secondary ID: 2013-004820-12U1
• Status: Completed
• Phase: Phase 1
• Start date: September 18, 2014
• Est. completion date: March 6, 2015

Study information

• Verified date: February 2020
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 32
• Est. completion date: March 6, 2015
• Est. primary completion date: March 6, 2015
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Diabetes
• Healthy

Intervention

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
• 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.
• 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.
• 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.

Locations

Country	Name	City	State
Germany	Novo Nordisk Investigational Site	Berlin

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Country where clinical trial is conducted

Germany, 

References & Publications (1)

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Area under the metformin plasma concentration-time curve		During a dosing interval (0 to12 hours) at steady state
Primary	Area under the digoxin plasma concentration-time curve		From time 0 to infinity after single dose
Secondary	Maximum observed metformin plasma concentration		During a dosing interval (0 to 12 hours) at steady state
Secondary	Maximum observed digoxin plasma concentration		0 to 120 hours after single dose
Secondary	Maximum observed semaglutide plasma concentration		During a dosing interval (0 to 24 hours) at steady state
Secondary	Area under the SNAC plasma concentration-time curve		During a dosing interval (0 to 24 hours) at steady state
Secondary	Number of hypoglycaemic episodes		From the first dosing (Day 1) and until completion of the post treatment follow up visit (Day 118-122)

External Links

•   Clinical Trials at Novo Nordisk