A Research Study Looking Into the Effect of Semaglutide and NNC0480 0389 on Blood Levels of a Birth Control Pill in Woman After Menopause

Investigation of the Effect of Subcutaneously Co-administered Semaglutide and NNC0480-0389 on Pharmacokinetics of an Oral Combination Contraceptive (Ethinylestradiol and Levonorgestrel) in Healthy Postmenopausal Females

Novo Nordisk is developing a combination therapy with the investigational drug NNC0480-0389 and an already approved medicine called "semaglutide" for the treatment of type-2 diabetes (T2D). It is expected that the combination will further improve the blood sugar control compared to semaglutide therapy alone. The study will investigate the influence of the combination of semaglutide and NNC0480-0389 on the blood levels of a birth control pill (a combined oral contraceptive consisting of ethinylestradiol and levonorgestrel) and paracetamol. Participants will get semaglutide and NNC0480-0389 as injection under the skin of their belly using a pen-injector. The injections will be given once weekly for 14 weeks. Additionally, participants will at two occasions get paracetamol as soluble tablet in connection with a standardised breakfast meal. Further, participants will get the birth control pill in form of tablets in two periods of 8 days each. Participants will get the combination of semaglutide and NNC0480-0389 as well as paracetamol and the combined contraceptive in any case. The study participation will last up to about 24 weeks. Participants will have 25 visits at the study centre. For 4 of the visits participants will stay at the study centre; the remaining visits will be outpatient. Only healthy postmenopausal women can take part in this study.

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Semaglutide 1.34 mg/mL; Drug: Semaglutide 3.0 mg/mL; Drug: NNC0480-0389 10 mg/mL; Drug: NNC0480-0389 30 mg/mL; Drug: Microgynon®

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • Novo Nordisk Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Postmenopausal female, aged greater than or equal to 45 years at the time of signing informed consent
• Body mass index between 20.0 and 29.9 kilogram per meter square (kg/m^2) (both inclusive)
• 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:

• Any disorder which in the investigator's opinion might jeopardise participant's safety or compliance with the protocol
• HbA1c greater than or equal to 6.5 % (48 millimoles per mole (mmol/mol)) at screening
• Use of prescription medicinal products or non-prescription drugs including any herbal medicine known to interfere with the metabolic cytochrome P450 enzyme (CYP) pathways, such as hypericum (St. John's Wort), ginseng, garlic, milk thistle, and echinaceae, within 14 days before screening. Exceptions are routine vitamins, occasional use of paracetamol, ibuprofen and acetylsalicylic acid, or topical medication not reaching systemic circulation
• Use of hormone replacement therapy within 4 weeks before first dose of trial product or intention to initiate treatment with hormone replacement therapy during the study
• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, cardiovascular, gastrointestinal, or endocrinological conditions

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Sequential Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: One-sequence cross-over arm

Drug: Semaglutide 1.34 mg/mL; Semaglutide will be administered at a dose of 0.25, 0.50 or 1.0 mg as indicated on scale drum once weekly by subcutaneous (s.c.) (under the skin) injections in the abdomen for 14 weeks.; Drug: Semaglutide 3.0 mg/mL; Semaglutide will be administered at a dose of 2.0 mg corresponding to the increment of 67 (pen injector units) as indicated on scale drum. once weekly by subcutaneous (s.c.) (under the skin) injections in the abdomen for 14 weeks.; Drug: NNC0480-0389 10 mg/mL; NNC0480-0389 will be administered at a dose of 0.23, 0.45 or 0.90 mL once weekly by s.c. (under the skin) injections for 14 weeks.; Drug: NNC0480-0389 30 mg/mL; NNC0480-0389 will be administered at a dose of 0.60 mL once weekly by s.c. (under the skin) injections for 14 weeks.; Drug: Microgynon®; Microgyn® will be given as once daily oral dosing in two periods, each of 8 days' duration. One tablet contains levonorgestrel 0.15 mg and ethinylestradiol 0.03 mg.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Area under the ethinylestradiol plasma concentration time curve during a dosing interval (0 to 24 hours) at steady state (AUC0-24h,EE,SS)	Measured in h*pg/mL	From pre-dose to 24 hours after last dosing of oral contraceptive on day 8 and day 100
Area under the levonorgestrel plasma concentration time curve during a dosing interval (0 to 24 hours) at steady state (AUC0-24h,LN,SS)	Measured in h*pg/mL	From pre-dose to 24 hours after last dosing of oral contraceptive on day 8 and day 100

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum concentration of ethinylestradiol at steady state (Cmax,EE,SS)	Measured in pg/mL	Within pre-dose to 24 hours after last dosing of oral contraceptive on day 8 and day 100
Maximum concentration of levonorgestrel at steady state (Cmax,LN,SS)	Measured in pg/mL	Within pre-dose to 24 hours after last dosing of oral contraceptive on day 8 and day 100
Area under the paracetamol concentration-time curve for 0-60 minutes following a standardised meal (AUC0-60min,para)	Measured in h*μg/mL	From pre-dose to 60 minutes after dosing of paracetamol on day 1 and day 93
Area under the paracetamol concentration-time curve for 0-300 minutes following a standardised meal (AUC0-300min,para)	Measured in h*μg/mL	From pre-dose to 300 minutes after dosing of paracetamol on day 1 and day 93
Maximum observed paracetamol concentration following a standardised meal (Cmax,para)	Measured in μg/mL	Within pre-dose to 300 minutes after dosing of paracetamol on day 1 and day 93

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S
• Investigators: Study Director: Clinical Transparency dept. 1452, Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): December 13, 2021
• Primary Completion (Actual): August 13, 2022
• Study Completion (Actual): September 1, 2022

Study Registration Dates

• First Submitted: December 8, 2021
• First Submitted That Met QC Criteria: December 8, 2021
• First Posted (Actual): December 10, 2021

Study Record Updates

• Last Update Posted (Estimated): November 13, 2023
• Last Update Submitted That Met QC Criteria: November 10, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Glucose Metabolism Disorders; Metabolic Diseases; Endocrine System Diseases; Diabetes Mellitus; Diabetes Mellitus, Type 2; Physiological Effects of Drugs; Contraceptive Agents, Hormonal; Contraceptive Agents; Reproductive Control Agents; Contraceptives, Oral, Combined; Contraceptives, Oral; Contraceptive Agents, Female; Contraceptives, Oral, Synthetic; Contraceptives, Oral, Hormonal; Contraceptives, Postcoital, Synthetic; Contraceptives, Postcoital; Contraceptives, Postcoital, Hormonal; Ethinyl estradiol, levonorgestrel drug combination; Ethinyl Estradiol-Norgestrel Combination
• Other Study ID Numbers: NN9389-4681; 2021-003060-27 (EudraCT Number); U1111-1266-3910 (Other Identifier: WHO)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: According to the Novo Nordisk disclosure commitment on novonordisk-trials.com

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No