A Research Study of How a New Medicine NNC0148-0287 C (Insulin 287) Works in the Body of People With Kidney Problems

Investigation of Pharmacokinetics and Safety Profile of a Single Dose NNC0148-0287 C (Insulin 287) in Subjects With Various Degrees of Renal Impairment

This study will be conducted to look at the effect of decreased kidney function when getting one dose of insulin 287 and to guide dosing recommendations in people who have altered kidney function. Insulin 287 works in the body for a long time (long-acting). It is taken once a day by injecting under the skin. The main target patient group for insulin 287 is people with type 2 diabetes. Participants will get just one injection. The study will last for up to 80 days. Participants will have 11 out-patient visits with the study doctor and one in-house visit of 3 days and 2 nights. Participants will have some assessments like several blood draws, electrocardiograms (ECGs), urine collections and capillary blood sugar tests. Participants cannot take part if they are hypersensitive to the study medicine, if they received any investigational product within 90 days before screening, or if they have certain diseases e.g. HIV or hepatitis or heart problems. Participants have to take photos if they experience any allergic reactions and send them to their study doctor. Participants' kidney function will be examined by a so called "Iohexol test".

Study Overview

• Status: Completed
• Conditions: Diabetes Mellitus, Type 2
• Intervention / Treatment: Drug: Insulin icodec

• Study Type: Interventional
• Enrollment (Actual): 58
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • 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, aged 18-75 years (both inclusive) at the time of signing informed consent.
• Body mass index between 18.5 and 32.0 kg/sqm (both inclusive).
• Meeting the pre-defined Glomerular Filtration Rate (GFR) values based on a measured GFR using an exogenous substance as tracer (renal group 1-4) or being in treatment with haemodialysis (renal group 5).

Exclusion Criteria:

• Known or suspected hypersensitivity to trial product or related products.
• Impaired liver function defined as Alanine Aminotransferase (ALT) greater than or equal to 2.5 times or Bilirubin greater than 1.5 times upper limit of normal at screening.
• Drugs known to affect creatinine clearance including cephalosporin and aminoglycoside antibiotics, flucytosine, cisplatin, cimetidine and trimethoprim within 14 days or 5 half-lives prior to the day of dosing of IMP.
• Renal group 1 (healthy subjects) exclusively: Unwilling to avoid use of prescription medicinal products or non-prescription drugs, except routine use of vitamins, occasional use of paracetamol, topical medication and contraceptives, within 14 days prior to the day of dosing.
• Renal Group 2-5 (renal impairment) exclusively: 1) Any disorder, except for conditions associated with renal impairment in the groups of subjects with reduced renal function, which in the investigator's opinion might jeopardise subject's safety, evaluation of results, or compliance with the protocol. Subjects with heart failure of functional class III-IV according to New York Heart Association (NYHA), subjects with Chronic obstructive pulmonary disease (COPD) grade 4 according to Global Initiative on Obstructive Lung Disease (GOLD), subjects with asthma step 5 according to Global Initiative for Asthma (GINA), subjects diagnosed with diabetes, subjects with uncontrolled treated/untreated hypertension (systolic blood pressure greater than or equal to 180 mmHg and /or diastolic blood pressure greater than or equal to 100 mmHg assessed in supine position) and other co-morbidities in terminal stages or which are decompensated or unstable should not be included in the study. 2) Subject requiring haemodialysis treatment unable or unwilling to undergo haemodialysis scheduled according to the standard clinical regimen throughout the trial period.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Participants with normal renal function; Participants with normal renal function (glomerular filtration rate [GFR] of greater than or equal to 90 ml/min) will receive single dose of insulin 287 on Day 1.	Drug: Insulin icodec; Participants will receive single dose of Insulin 287 subcutaneously (under the skin) on Day 1; Other Names: Insulin 287
Experimental: Participants with mildly decreased renal function; Participants with mildly decreased renal function (GFR of 60 to less than 90 ml/min) will receive single dose of insulin 287 on Day 1.	Drug: Insulin icodec; Participants will receive single dose of Insulin 287 subcutaneously (under the skin) on Day 1; Other Names: Insulin 287
Experimental: Participants with moderately decreased renal function; Participants with moderately decreased renal function (GFR of 30 to less than 60 ml/min) will receive single dose of insulin 287 on Day 1.	Drug: Insulin icodec; Participants will receive single dose of Insulin 287 subcutaneously (under the skin) on Day 1; Other Names: Insulin 287
Experimental: Participants with severely decreased renal function; Participants with severely decreased renal function (GFR of less than 30 not requiring dialysis) will receive single dose of insulin 287 on Day 1.	Drug: Insulin icodec; Participants will receive single dose of Insulin 287 subcutaneously (under the skin) on Day 1; Other Names: Insulin 287
Experimental: Participants with end-stage renal disease; Participants with end-stage renal disease requiring haemodialysis will receive single dose of insulin 287 on Day 1.	Drug: Insulin icodec; Participants will receive single dose of Insulin 287 subcutaneously (under the skin) on Day 1; Other Names: Insulin 287

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUCI287,0-840h,SD: Area under the serum insulin 287 concentration-time curve after a single dose	Measured in pmol*h/L	From 0 to 840 hours after trial product administration (visit 2 (study day 1))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cmax,I287,SD: Maximum observed serum insulin 287 concentration after a single dose	Measured in pmol/L	From 0 to tz hours after trial product administration (visit 2 (study day 1)), where tz is the time of the last quantifiable concentration
tmax,I287,SD: Time to maximum observed serum insulin 287 concentration after a single dose	Measured in hours	From 0 to tz hours after trial product administration (visit 2 (study day 1)).
Number of adverse events	Number of events	From trial product administration (visit 2 (study day 1)) until visit 13 (study day 43)
Change in anti-insulin 287 antibody level	Measured in % B/T (percentage of bound tracer measured after precipitation to total tracer)	From visit 2 (study day 1, pre-dose) to visit 13 (study day 43)
Change in anti-insulin 287 antibody titres	Number of dilutions	From visit 2 (study day 1, pre-dose) to visit 13 (study day 43)
Positive cross-reactive anti-human insulin antibodies	Number of patients with/without positive cross-reactive anti-human insulin antibodies	At visit 13 (study day 43)

Collaborators and Investigators

• Sponsor: Novo Nordisk A/S

Study record dates

Study Major Dates

• Study Start (Actual): November 9, 2018
• Primary Completion (Actual): September 6, 2019
• Study Completion (Actual): September 6, 2019

Study Registration Dates

• First Submitted: October 26, 2018
• First Submitted That Met QC Criteria: October 26, 2018
• First Posted (Actual): October 30, 2018

Study Record Updates

• Last Update Posted (Actual): March 8, 2021
• Last Update Submitted That Met QC Criteria: March 5, 2021
• Last Verified: March 1, 2021

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; Hypoglycemic Agents; Physiological Effects of Drugs; Insulin; Insulin, Globin Zinc
• Other Study ID Numbers: NN1436-4226; 2017-004529-34 (EudraCT Number); U1111-1204-8972 (Other Identifier: World Health Organization)

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