A trial comparing efficacy and safety of semaglutide once-weekly versus placebo as add-on to basal insulin alone or basal insulin in combination with metformin in subjects with type 2 diabetes

• Register: EUCTR
• Last refreshed on: 7 December 2015
• Main ID: EUCTR2013-004502-26-DE
• Date of registration: 23/07/2014
• Prospective Registration: Yes
• Primary sponsor: Novo Nordisk A/S
• Public title: A trial comparing efficacy and safety of semaglutide once-weekly versus placebo as add-on to basal insulin alone or basal insulin in combination with metformin in subjects with type 2 diabetes
• Scientific title: Efficacy and safety of semaglutide once-weekly versus placebo as add-on to basal insulin alone or basal insulin in combination with metformin in subjects with type 2 diabetes - SUSTAIN™ 5 – Add on to Basal Insulin
• Date of first enrolment: 09/09/2014
• Target sample size: 390
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2013-004502-26
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 4

Countries of recruitment

European Union, Germany, Japan, Serbia, Slovakia, United States

Contacts

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

• Name: Global Clinical Registry (GCR,1452)
• Affiliation: Novo Nordisk A/S

Key inclusion & exclusion criteria

Inclusion criteria:
1. Male or female, age =18 years at the time of signing inform consent. For Japan: Male or female, age =20 years at the time of signing informed consent.
2. Subjects diagnosed with T2DM and on stable diabetes treatment (+/- 20% change in total daily dose) with basal insulin (minimum of 0.25 IU/kg/day and/or 20 IU/day of: insulin glargine, insulin detemir, insulin degludec and/or NPH insulin ) alone or in combination with metformin (minimum of 1500 mg/day or maximal tolerable dose) for 90 days prior to screening.
3. HbA1c 7.0 – 10.0% (53 - 86 mmol/mol) both inclusive.
Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 292
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 98

Exclusion criteria:
1. Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method throughout the trial including the 5 weeks follow-up period (adequate contraceptive measures as required by local regulation or practice). Germany: Only highly effective methods of birth control are accepted (ie one that results in less than 1% per year failure rate when used consistently and correctly such as implants, injectables, combined oral contraceptives, some intrauterine device), or sexual abstinence or vasectomised partner. Japan: Adequate contraceptive measures are abstinence (not having sex), diaphragm, condom (by the partner), intrauterine device, sponge, spermicide or oral contraceptives.
2. Treatment with any glucose lowering agents other than stated in the inclusion criteria in a period of 90 days before screening. An exception is short-term treatment (=7 days in total) with bolus insulin in connection with intercurrent illness.
3. Experienced more than 3 episodes of severe hypoglycaemia within 6 months prior to screening, and/or hypoglycaemia unawareness.
4. History of pancreatitis (acute or chronic).
5. Screening calcitonin value =50 ng/L (pg/mL).
6. Personal or family history of medullary thyroid carcinoma (MTC) or multiple endocrine neoplasia syndrome 2 (MEN 2).
7. Severe renal impairment defined as eGFR < 30 mL/min/1.73 m^2 per Modification of Diet in Renal Disease (MDRD) formula (4 variable version). For Germany only: For subjects on metformin moderate renal impariment defined as eGFR < 60 mL/min/1.73 m^2 per MDRD formula (4 variable version) and for subjects not on metformin severe renal impairment defined as eGFR < 30 mL/min/1.73 m^2 per MDRD formula (4 variable version).
8. Acute coronary or cerebrovascular event within 90 days before randomisation.
9. Heart failure, New York Heart Association (NYHA) Class IV.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Diabetes Mellitus, Type 2
MedDRA version: 18.0 Level: LLT Classification code 10045242 Term: Type II diabetes mellitus System Organ Class: 100000004861

Therapeutic area: Diseases [C] - Nutritional and Metabolic Diseases [C18]

Intervention(s)

Product Name: Semaglutide B 1.34 mg/ml PDS290
Pharmaceutical Form: Solution for injection
INN or Proposed INN: SEMAGLUTIDE
CAS Number: 910463-68-2
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 1.34-
Pharmaceutical form of the placebo: Solution for injection in pre-filled pen
Route of administration of the placebo: Subcutaneous use

Primary Outcome(s)

Secondary Objective: To compare the effect of once-weekly dosing of two dose levels of semaglutide (0.5 mg and 1.0 mg) versus placebo in subjects with type 2 diabetes mellitus on basal insulin with regards to:
- Inducing and maintaining weight loss
- Other parameters of efficacy, safety, tolerability and patient reported outcomes

Timepoint(s) of evaluation of this end point: From baseline to week 30

Main Objective: To demonstrate superiority of once-weekly dosing of two dose levels (0.5 mg and 1.0 mg) of semaglutide versus placebo on glycaemic control in subjects with type 2 diabetes mellitus on basal insulin.

Primary end point(s): Change in HbA1c

Secondary Outcome(s)

Timepoint(s) of evaluation of this end point: 1-6. From baseline to week 30
7-8. After 30 weeks treatment

Secondary end point(s): Change in:
1. Body weight
2. Fasting plasma glucose (FPG)
3. Insulin dose
4. Systolic and diastolic blood pressure
5. Patient reported outcomes, Diabetes Treatment Satisfaction Questionnaire (DTSQ)

Subjects who achieve (yes/no):
7. HbA1c <7.0% (53 mmol/mol) American Diabetes Association (ADA) target
8. HbA1c =6.5% (48 mmol/mol) American Association of Clinical Endocrinologists (AACE) target

Secondary ID(s)

NN9535-3627

Source(s) of Monetary Support

Novo Nordisk A/S