A Randomised Controlled Clinical Trial in Type 2 Diabetes Comparing Semaglutide to Placebo and Liraglutide

Diabetes Mellitus, Type 2 Clinical Trial

Official title:

Investigation of Safety and Efficacy of Five Doses of Semaglutide Versus Placebo and Open-label Liraglutide, as Add on Therapy, in Subjects Diagnosed With Type 2 Diabetes Currently Treated With Metformin or Controlled With Diet and Exercise A 12 Week Multi-centre, Multi National, Double-blind, Placebo-controlled, Randomised, Nine Armed Parallel Group, Dose Finding Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00696657
• Other study ID #: NN9535-1821
• Secondary ID: 2007-003956-12
• Status: Completed
• Phase: Phase 2
• Start date: June 3, 2008
• Est. completion date: February 5, 2009

Study information

• Verified date: July 2019
• Source: Novo Nordisk A/S
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial was conducted in Europe,Asia and Africa. Study participants were randomised evenly to treatment with semaglutide (0.1 mg QW - 1.6 mg QW, 6 treatment arms, placebo or liraglutide (1.2 mg QD, or 1.8 mg QD).Treatment allocation to semaglutide or placebo was double-blind, whereas liraglutide treatment was administered open-label.Primary efficacy parameter was HbA1c and the treatment duration was 12 weeks.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 415
• Est. completion date: February 5, 2009
• Est. primary completion date: February 5, 2009
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Men and women-not-of-childbearing potential diagnosed with type 2 diabetes for at least three months

• Stable treatment regimen with either metformin (at least 1500 mg) or diet and exercise alone for at least three months

• HbA1c: 7.0-10.0 % (both inclusive)

• Body weight between 60 kg and 110 kg

Exclusion Criteria:

• Treatment with insulin, GLP-1 receptor agonists (including liraglutide), dipeptidyl peptidase-4 inhibitors, sulphonylurea, thiazolidinediones, Alpha-GIs, or any investigational drug, within the last three months

• Impaired liver or kidney function

• Proliferative retinopathy or maculopathy requiring acute treatment

• Clinically significant active cardiovascular disease and uncontrolled treated/untreated hypertension

• Recurrent major hypoglycaemia or hypoglycaemic unawareness

• Present or planned use of any drug which could interfere with the glucose levels (e.g. systemic corticosteroids)

Related Conditions & MeSH terms

• Diabetes
• Diabetes Mellitus
• Diabetes Mellitus, Type 2

Intervention

Drug:
• semaglutide
0.1 mg, once weekly, s.c. injection
• semaglutide
0.2 mg, once weekly, s.c. injection
• semaglutide
0.4 mg, once weekly, s.c. injection
• semaglutide
0.8 mg, once weekly, s.c. injection
• semaglutide
0.8 mg with titration, once weekly, s.c. injection
• semaglutide
1.6 mg with titration, once weekly, s.c. injection
• placebo
0.1 mg, once weekly, s.c. injection
• placebo
0.2 mg, once weekly, s.c. injection
• placebo
0.4 mg, once weekly, s.c. injection
• placebo
0.8 mg with titration, once weekly, s.c. injection
• placebo
1.6 mg, once weekly, s.c. injection
• liraglutide
1.2 mg with titration, once daily, s.c. injection
• liraglutide
1.8 mg with titration, once daily, s.c. injection

Locations

Country	Name	City	State
Austria	Novo Nordisk Investigational Site	Gratwein
Austria	Novo Nordisk Investigational Site	Graz
Austria	Novo Nordisk Investigational Site	Innsbruck
Austria	Novo Nordisk Investigational Site	Mödling
Austria	Novo Nordisk Investigational Site	Wien
Austria	Novo Nordisk Investigational Site	Wien
Austria	Novo Nordisk Investigational Site	Wien
Austria	Novo Nordisk Investigational Site	Wien
Bulgaria	Novo Nordisk Investigational Site	Plovdiv
Bulgaria	Novo Nordisk Investigational Site	Russe
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Sofia
Bulgaria	Novo Nordisk Investigational Site	Varna
Finland	Novo Nordisk Investigational Site	Helsinki
Finland	Novo Nordisk Investigational Site	Imatra
Finland	Novo Nordisk Investigational Site	Mikkeli
Finland	Novo Nordisk Investigational Site	Oulu
Finland	Novo Nordisk Investigational Site	Tampere
Finland	Novo Nordisk Investigational Site	Turku
Former Serbia and Montenegro	Novo Nordisk Investigational Site	Belgrade
France	Novo Nordisk Investigational Site	Dommartin Les Toul
France	Novo Nordisk Investigational Site	LA ROCHELLE cedex
France	Novo Nordisk Investigational Site	MONTPELLIER cedex 5
France	Novo Nordisk Investigational Site	Narbonne
France	Novo Nordisk Investigational Site	Venissieux
Germany	Novo Nordisk Investigational Site	Bad Lauterberg
Germany	Novo Nordisk Investigational Site	Falkensee
Germany	Novo Nordisk Investigational Site	Hamburg
Germany	Novo Nordisk Investigational Site	Ludwigshafen
Germany	Novo Nordisk Investigational Site	Marburg
Germany	Novo Nordisk Investigational Site	Münster
Germany	Novo Nordisk Investigational Site	Pohlheim
Hungary	Novo Nordisk Investigational Site	Budapest
Hungary	Novo Nordisk Investigational Site	Debrecen
Hungary	Novo Nordisk Investigational Site	Gyula
Hungary	Novo Nordisk Investigational Site	Pecs
Hungary	Novo Nordisk Investigational Site	Szekszárd
India	Novo Nordisk Investigational Site	Chennai	Tamil Nadu
India	Novo Nordisk Investigational Site	Chennai
India	Novo Nordisk Investigational Site	Hyderabad
India	Novo Nordisk Investigational Site	Hyderabad	Andhra Pradesh
Italy	Novo Nordisk Investigational Site	Catanzaro
Italy	Novo Nordisk Investigational Site	Chieti
Italy	Novo Nordisk Investigational Site	Firenze
Italy	Novo Nordisk Investigational Site	Milano (MI)
Italy	Novo Nordisk Investigational Site	Napoli
Italy	Novo Nordisk Investigational Site	Perugia
South Africa	Novo Nordisk Investigational Site	Cape Town	Western Cape
South Africa	Novo Nordisk Investigational Site	Durban	KwaZulu-Natal
South Africa	Novo Nordisk Investigational Site	Pretoria	Gauteng
Spain	Novo Nordisk Investigational Site	Almería
Spain	Novo Nordisk Investigational Site	Gijón
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Madrid
Spain	Novo Nordisk Investigational Site	Sevilla
Spain	Novo Nordisk Investigational Site	Valencia
Switzerland	Novo Nordisk Investigational Site	Bern
Switzerland	Novo Nordisk Investigational Site	Genève 14
Switzerland	Novo Nordisk Investigational Site	Lausanne
Switzerland	Novo Nordisk Investigational Site	St. Gallen
Turkey	Novo Nordisk Investigational Site	Antalya
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
Turkey	Novo Nordisk Investigational Site	Istanbul
United Kingdom	Novo Nordisk Investigational Site	Addlestone
United Kingdom	Novo Nordisk Investigational Site	Bath
United Kingdom	Novo Nordisk Investigational Site	Bexhill-on-Sea
United Kingdom	Novo Nordisk Investigational Site	Bradford
United Kingdom	Novo Nordisk Investigational Site	Dundee
United Kingdom	Novo Nordisk Investigational Site	Guildford
United Kingdom	Novo Nordisk Investigational Site	Hull
United Kingdom	Novo Nordisk Investigational Site	Inverness
United Kingdom	Novo Nordisk Investigational Site	Llanelli
United Kingdom	Novo Nordisk Investigational Site	Sheffield
United Kingdom	Novo Nordisk Investigational Site	Trowbridge

Sponsors (1)

Lead Sponsor	Collaborator
Novo Nordisk A/S

Countries where clinical trial is conducted

Austria,  Bulgaria,  Finland,  Former Serbia and Montenegro,  France,  Germany,  Hungary,  India,  Italy,  South Africa,  Spain,  Switzerland,  Turkey,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	HbA1c	Change from baseline in HbA1c was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the last observation carried forward (LOCF) approach.	After 12 weeks of treatment.
Secondary	Percentage of Subjects With an Adverse Events	The results of adverse event presented here are treatment emergent, i.e., TEAE. A TEAE was defined as an event that had onset on or after the first date (week 0) on trial product and no later than 5 weeks after the last date on trial product (week 17), or that had onset before the first date on trial product and increases in severity during the treatment period until 5 weeks after the last date on trial product.	After 12 weeks of treatment.
Secondary	Percentage of Subjects With Hypoglycaemic Episode	The results of hypoglycaemic episode presented here are treatment emergent. Hypoglycaemic episodes were defined as treatment emergent if they had onset on or after the first day of randomised treatment (in week 0) and no later than 5 weeks after the last date on trial product (week 17). Hypoglycaemic episodes are classified as follows: Major: If the subject was not able to treat himself or herself and was needed to be administered food, glucagon or intravenous (i.v.) glucose by another person. Minor: If the subject was able to treat himself or herself and measured plasma glucose was <3.1 mmol/L (56 mg/dL). Symptoms only: If the subject was able to treat himself or herself and measured plasma glucose was >=3.1 mmol/L (56 mg/dL) or no plasma glucose measurement was done.	After 12 weeks of treatment
Secondary	Change From Baseline in ECG	A standard 12 lead electrocardiogram (ECG) with a 10-second rhythm strip was performed at screening (week -2) and at the end of treatment (week 12). The time frame should be read as "week -2, week 12". Change from baseline in ECG was measured in terms of number of subjects in each category (normal, abnormal, not clinically significant [NCS] or abnormal clinically significant [CS]) at week -2 and week 12 (i.e., change in each category in terms of number of subjects from week -2 to week 12).	Week 0, week 12.
Secondary	Change From Baseline in Vital Signs (Pulse)	Change from baseline in pulse was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Vital Signs (Blood Pressure; SBP)	Change from baseline in systolic blood pressure (SBP) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Vital Signs (Blood Pressure; DBP)	Change from baseline in diastolic blood pressure (DBP) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Basophils)	Change from baseline in basophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Eosinophils)	Change from baseline in eosinophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Haematocrit)	Change from baseline in haematocrit (the proportion of blood that consists of red blood cells) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Haemoglobin)	Change from baseline in haemoglobin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Lymphocytes)	Change from baseline in lymphocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Monocytes)	Change from baseline in monocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Neutrophils)	Change from baseline in neutrophils was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Thrombocytes)	Change from baseline in thrombocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Erythrocytes)	Change from baseline in erythrocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Haematology; Leukocytes)	Change from baseline in leukocytes was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Albumin)	Change from baseline in albumin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Alkaline Phosphatase)	Change from baseline in alkaline phosphatase was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; AST)	Change from baseline in aspartate aminotransferase (AST) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; ALAT)	Change from baseline in alanine aminotransferase (ALAT) was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Total Bilirubin)	Change from baseline in total bilirubin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Calcium, Total)	Change from baseline in calcium, total was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Calcium, Ionised)	Change from baseline in calcium, ionised was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Creatinine)	Change from baseline in creatinine was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Potassium)	Change from baseline in potassium was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Sodium)	Change from baseline in sodium was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Biochemistry; Urea)	Change from baseline in urea was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Glucose)	Change from baseline in urine-glucose was measured in terms of number of subjects in each category (negative, positive, >=55 mmol/L, or missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Haemoglobin)	Change from baseline in urine-haemoglobin was measured in terms of number of subjects in each category (negative, trace, small, moderate/large and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Ketones)	Change from baseline in urine-ketone was measured in terms of number of subjects in each category (negative, positive, >=55 mmol/L and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; pH)	Change from baseline in urine-pH was measured in terms of number of subjects in each category (pH=6.0, 6.5, 7.0, 7.5, 8.0, >=8.5 and missing) at week 0 and week 12 (i.e., change in each category in terms of number of subjects from week 0 to week 12).	Week 0, week 12
Secondary	Change From Baseline in Standard Safety Laboratory Parameter (Urinalysis; Protein)	Change from baseline in urine-protein was measured in terms of number of subjects in each category at week 0 (negative, 0.3 g/L, 1.0 g/L and missing) and week 12 (negative, trace, 0.3 g/L, 1.0 g/L, >=3.0 g/L and missing). i.e., change in each category in terms of number of subjects from week 0 to week 12.	Week 0, week 12
Secondary	Change From Baseline in Calcitonin	Change from baseline in calcitonin was evaluated after 12 weeks of treatment. Post baseline (week 0) missing values were replaced using the LOCF approach.	Week 0, week 12.
Secondary	Percentage of Subjects Developing Anti-semaglutide Antibodies	Antibodies were measured after 12-week of treatment at week 17; percentage of participants with positive anti-semaglutide antibodies are presented here. Assessments of antibodies were not done for subjects allocated to the open-label liraglutide treatment arms.	After 12 weeks of treatment

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