A Research Study of How Overdosing of a New Once Weekly Medicine NNC0148-0287 C (Insulin 287) Influences the Blood Sugar Level in People With Type 2 Diabetes

NCT03945656 | Completed Phase 1

• 3 other identifiers: NN1436-4462U1111-1214-26882018-001993-74
• Study Type: interventional
• Target: 43
• Locations: 1 country
• Sites: 1

Brief Summary

This study is comparing the effect of a long-acting insulin analogue (insulin 287) with insulin glargine (Lantus®) in subjects with type 2 diabetes. In addition, the study is looking at symptoms of low blood sugar, awareness of low blood sugar and the time and amount of glucose needed to recover from low blood sugar after injecting 2 and 3 times the basal dose of insulin 287 and glargine. The purpose of the study is to make a once-weekly injectable basal insulin treatment for people with type 2 diabetes. Participants will get insulin 287 as well as insulin glargine - which treatment any participant gets first is decided by chance. Insulin 287 is a new medicine; insulin glargine can already be prescribed. The study medicines will be in a pen, and must be injected with a needle in the thigh once per day (insulin glargine) or once per week (insulin 287). The study will last for minimum 3 months and up to approximately 6 months. Participants will have 21 clinic visits and at least 2 phone calls with the study doctor. The participants' health will be monitored carefully and blood samples will be taken at the clinic visits.

Conditions

Diabetes Mellitus, Type 2

Outcome Measures

Primary Outcomes (1)

• Clinically significant hypoglycaemia (Double dose): Clinically significant hypoglycaemia (Plasma glucose [PG] less than 3.0 mmol/L [54 mg/dL]) after 2 times the individualised optimal basal dose of insulin

  Yes/No Blood sugar lower than 3.0 mmol/L (54 mg/dL) after receiving a double dose of basal insulin Number of subjects experiencing an event is to be reported

  From start of hypoglycaemia induction after 2 times the individualised optimal basal dose of insulin (day 17 for insulin 287, day 4 for insulin glargine) until termination of the clamp the following day

Secondary Outcomes (21)

• PG (nadir) - PG concentration at nadir after 2 and 3 times the individualised optimal basal dose of insulin

  From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day

• t (decline, PG 5.5 mmol/L - PG 3.0 mmol/L) - Time from start of hypoglycaemia induction until a PG concentration of 3.0 mmol/L (54 mg/dL) is reached after 2 and 3 times the individualised optimal basal dose of insulin

  From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day

• t (decline, PG 5.5 mmol/L - PG nadir) - Time from start of hypoglycaemia induction until PGnadir is reached after 2 and 3 times the individualised optimal basal dose of insulin

  From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day

• t (recovery, PG nadir - PG 5.5 mmol/L) - Time to increase from PGnadir to a PG concentration of 5.5 mmol/L (100 mg/dL) after 2 and 3 times the individualised optimal basal dose of insulin

  From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day

• C (glucagon, PG nadir) - Plasma glucagon concentration at PGnadir after 2 and 3 times the individualised optimal basal dose of insulin

  From start of hypoglycaemia induction after 2 and 3 times the individualised optimal basal dose of insulin (day 17/day 38 for insulin 287, day 4/day 11 for insulin glargine) until termination of the clamp the following day

Study Arms (2)

Insulin 287 followed by insulin glargine

EXPERIMENTAL

Run-in period (3 to 28 days): Once daily insulin glargine treatment with or without any usual metformin treatment. After run-in, participants will receive insulin 287 once a week (OW) for 6 weeks. After insulin 287 treatment, participants will receive insulin glargine U100 OD for 12 days.

Drug: insulin icodec; Drug: Insulin glargine

Insulin glargine followed by insulin 287

ACTIVE COMPARATOR

Run-in period (3 to 28 days): Once daily insulin glargine treatment with or without any usual metformin treatment. After run-in, participants will receive insulin glargine U100 OD for 12 days. After insulin glargine treatment, participants will receive insulin 287 OW for 6 weeks.

Drug: insulin icodec; Drug: Insulin glargine

Interventions

insulin icodec DRUG

Participants will receive subcutaneous (s.c.) injections of insulin 287 OW for 6 weeks

Also known as: Insulin 287

Insulin 287 followed by insulin glargine; Insulin glargine followed by insulin 287

Insulin glargine DRUG

Participants will receive daily s.c. injections of insulin glargine U100 for 12 days

Insulin 287 followed by insulin glargine; Insulin glargine followed by insulin 287

Eligibility Criteria

• Age: 18 Years - 72 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female, aged between 18 and 72 years (both inclusive) at the time of signing informed consent.
• Body mass index between 18.5 and 37.9 kg/m\^2 (both inclusive).
• Diagnosed with type 2 diabetes mellitus greater than or equal to 180 days prior to the day of screening.
• Glycosylated haemoglobin type A1c (HbA1c) less than or equal to 9.0% (less than or equal to 74 mmol/mol) at screening.
• Current total daily insulin treatment between 0.2 and 1.0 U/kg/day (both inclusive).

You may not qualify if:

• Known or suspected hypersensitivity to trial products or related products.
• Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method.
• Presence or history of any clinically relevant respiratory, metabolic, renal, hepatic, gastrointestinal, endocrinological conditions (except conditions associated with diabetes mellitus).

Sponsors & Collaborators

• Novo Nordisk A/S: lead

Study Sites (1)

Novo Nordisk Investigational Site

Graz, 8010, Austria

Location

Related Publications (1)

• Pieber TR, Arfelt KN, Cailleteau R, Hart M, Kar S, Mursic I, Svehlikova E, Urschitz M, Haahr H. Hypoglycaemia frequency and physiological response after double or triple doses of once-weekly insulin icodec vs once-daily insulin glargine U100 in type 2 diabetes: a randomised crossover trial. Diabetologia. 2023 Aug;66(8):1413-1430. doi: 10.1007/s00125-023-05921-8. Epub 2023 Jun 13.

  PMID: 37308751 BACKGROUND

MeSH Terms

Conditions

Diabetes Mellitus, Type 2

Interventions

insulin icodec; Insulin Glargine

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Insulin, Long-Acting; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Clinical Reporting Anchor and Disclosure (1452)

  Novo Nordisk A/S

  STUDY DIRECTOR

Study Design

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

Study Record Dates

• First Submitted: May 8, 2019
• First Posted: May 10, 2019
• Study Start: May 7, 2019
• Primary Completion: September 27, 2021
• Study Completion: September 27, 2021
• Last Updated: September 6, 2023

Record last verified: 2023-08

Data Sharing

• IPD Sharing: Will share

Locations

AU (1)