Clinical trial NCT04262661: A Study to Look at How Safe NNC0472-0147 is in Healthy People and in People With Type 2 Diabetes
Official title: A Trial Investigating the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Subcutaneous NNC0472-0147 in Healthy Subjects and in Subjects With Type 2 Diabetes Mellitus
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2020-02-10
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 64
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Part 1: Single ascending dose, placebo control. Part 2: Multiple ascending dose design, active control.
Primary purpose: TREATMENT

Brief summary: This study is investigating the safety and tolerability of the new medicine NNC0472-0147, its concentrations in the blood and its effect on blood sugar for the treatment of diabetes. Another goal of the study is to determine an effect of NNC0472-0147 on cholesterol. The first part of the study is conducted in healthy people, while the second part involves people with type 2 diabetes (T2DM). The study will test how NNC0472-0147 is tolerated by the body, how it is taken up in the blood, how long it stays there and how much blood sugar is lowered. In part 1, participants will either get the new medicine NNC0472-0147 or placebo (an injection that does not contain active medicine) - which treatment is decided by chance. In part 2, participants will either get the new medicine NNC0472-0147 or insulin glargine - which treatment is decided by chance. It is the first time that NNC0472-0147 is tested in humans. Participants will get once daily injections of either NNC0472-0147 or insulin glargine for a treatment period of fourteen days. The injections will be given under the skin (subcutaneously, s.c.) of the left thigh. Participants will be in the study for about 7 weeks. There will be 15 visits with the study doctor. People cannot be in the study if the study doctor thinks that there are risks for their health. Only women who cannot become pregnant are allowed to participate.


Eligibility criteria: Inclusion Criteria:

Part 1:

* Male
* Aged 18-55 years (both inclusive) at the time of signing nformed consent.

Part 2:

* Male, or female of non-child bearing potential. Non-child bearing potential is defined by being surgically sterilised (documented hysterectomy, bilateral salpingectomy or bilateral oophorectomy) or being postmenopausal (no menses for 12 months without an alternative medical cause) prior to the day of screening.
* Aged 18-64 years (both inclusive) at the time of signing informed consent.
* Diagnosed with T2DM at least 180 days prior to the day of screening.
* Treated with any insulin for 90 days or longer prior to the day of screening.
* Low-density lipoprotein cholesterol level above 1.80 mmol L.

Exclusion Criteria:

Part 1:

- Male of reproductive age who or whose partner(s) is not using highly effective contraceptive methods (highly effective contraceptive measures as required by local regulation or practice). Highly effective contraceptive measures include that the male subject uses a condom during intercourse and that the partner practices highly effective contraception (risk of pregnancy must be lower than 1%). In addition, subjects must not donate sperm for the duration of the trial.

Part 2:

* Male of reproductive age who or whose partner(s) is not using highly effective contraceptive methods (highly effective contraceptive measures as required by local regulation or practice). Highly effective contraceptive measures include that the male subject uses a condom during intercourse and that the partner practices highly effective contraception (risk of pregnancy must be lower than 1%). In addition, subjects must not donate sperm for the duration of the trial.
* Use of oral antidiabetic drugs (OADs) other than metformin or use of glucagon-like peptide-1 (GLP-1) receptor agonists (e.g. exenatide, liraglutide, semaglutide) within 90 days prior to the day of screening.
* Treatment with peptide proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors within 180 days prior to the day of screening.

Primary outcomes:
measure: Part 1: Number of treatment emergent adverse events
timeFrame: From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 15, visit 6)
measure: Part 2: Number of treatment emergent adverse events
timeFrame: From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 30, visit 14)
Secondary outcomes:
measure: Number of hypoglycaemic episodes of alert value (level 1) below 3.9 mmol/L (70 mg/dL) and equal to or above 3.0 mmol/L (54 mg/dL)
timeFrame: From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 15, visit 6)
measure: Number of hypoglycaemic episodes of alert value (level 1) below 3.9 mmol/L (70 mg/dL) and equal to or above 3.0 mmol/L (54 mg/dL)
timeFrame: From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 30, visit 14)
measure: Number of clinically significant hypoglycaemic episodes (level 2) below 3.0 mmol/L (54 mg/dL)
timeFrame: From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 15, visit 6)
measure: Number of clinically significant hypoglycaemic episodes (level 2) below 3.0 mmol/L (54 mg/dL)
timeFrame: From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 30, visit 14)
measure: Number of severe hypoglycaemic episodes (level 3)
timeFrame: From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 15, visit 6)
measure: Number of severe hypoglycaemic episodes (level 3)
timeFrame: From IMP administration at day 1 (visit 2) until completion of post-treatment end-of-trial visit (day 30, visit 14)
measure: Area under the serum NNC0472-0147 concentration-time curve after a single dose
timeFrame: From 0 hours until infinity after a single IMP administration at day 1 (visit 2).
measure: Maximum observed serum NNC0472-0147 concentration after a single dose
timeFrame: From 0 hours until last measurement time after a single IMP administration at day 1 (visit 2)
measure: Area under the serum NNC0472-0147 concentration-time curve during one dosing interval at steady state
timeFrame: From 0 to 24 hours after last multiple IMP administration at day 14 (visit 9)
measure: Maximum observed serum NNC0472-0147 concentration at steady state
timeFrame: From 0 to 24 hours after last multiple IMP administration at day 14 (visit 9)
Other outcomes:
Locations:
city: Mainz
country: Germany
facility: Novo Nordisk Investigational Site
city: Neuss
country: Germany
facility: Novo Nordisk Investigational Site
Study officials:
affiliation: Novo Nordisk A/S
name: Clinical Reporting Anchor & Disclosure (1452)
role: STUDY_DIRECTOR
References: