A Dose Finding Study to Assess the Effect of LIK066 Compared to Placebo or Empagliflozin in Patients With Type 2 Diabetes Mellitus and Heart Failure

NCT03152552 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: CLIK066B22042016-003084-19
• Study Type: interventional
• Target: 125
• Locations: 24 countries
• Sites: 106

Brief Summary

This was a dose-finding study to evaluate the efficacy, safety and tolerability of 3 different doses of LIK066 compared to placebo or empagliflozin in T2DM patients with heart failure

Conditions

Diabetes Mellitus and Heart Failure

Keywords

Diabetes mellitus; LIK066; Obesity; Type 2 diabetes mellitus (T2DM); Heart Failure (HF); Hypertension; Renal dysfunction; Adult-onset diabetes; Noninsulin-dependent diabetes mellitus (NIDDM); High blood sugar

Outcome Measures

Primary Outcomes (1)

• Change From Baseline in N-terminal Pro B-type Natriuretic Peptide (NT-proBNP) at Week 12

  Evaluation of NT-proBNP was performed by a central laboratory. For Change from baseline, Geometric mean is the geometric mean of the endpoint to baseline ratio. Pre-planned statistical analysis was not performed for this primary endpoint due to early study termination. Only descriptive statistics are presented.

  Baseline, Week 12

Secondary Outcomes (25)

• Change From Baseline in Glycated Hemoglobin (HbA1c) at Weeks 12 and 36

  Baseline, Week 12, Week 36

• Change From Baseline in Fasting Plasma Glucose (FPG) at Weeks 12 and 36

  Baseline, Week 12, Week 36

• Change From Baseline in Body Weight at Weeks 12 and 36

  Baseline, Week 12, Week 36

• Change From Baseline in Body Composition Assessed by Bio-impedance (Total Body Fat Mass) at Weeks 12 and 36

  Baseline, Week 12, Week 36

• Change From Baseline in Body Composition Assessed by Bio-impedance (Visceral Fat Level) at Weeks 12 and 36

  Baseline, Week 12, Week 36

Study Arms (5)

LIK066 2.5mg

EXPERIMENTAL

Eligible participants randomized to this treatment arm received the LIK066 2.5mg dose regimen once daily for 36 weeks.

Drug: LIK066

LIK066 10mg

EXPERIMENTAL

Eligible participants randomized to this treatment arm received the LIK066 10mg dose regimen once daily for 36 weeks.

Drug: LIK066

LIK066 50mg

EXPERIMENTAL

Eligible participants randomized to this treatment arm received the LIK066 50mg dose regimen once daily for 36 weeks.

Drug: LIK066

Empagliflozin

ACTIVE COMPARATOR

Participants randomized to this treatment arm received empagliflozin once daily for 36 weeks.

Drug: Empagliflozin

Placebo

PLACEBO COMPARATOR

Participants randomized to this treatment arm received LIK066 matching placebo and empagliflozin matching placebo.

Drug: Placebo

Interventions

LIK066 DRUG

LIK066 was supplied in different doses as tablets taken orally.

LIK066 10mg; LIK066 2.5mg; LIK066 50mg

Placebo DRUG

Placebo was supplied as tablets and capsules taken orally.

Placebo

Empagliflozin DRUG

Empagliflozin was supplied as capsules taken orally.

Empagliflozin

Eligibility Criteria

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

You may qualify if:

• BMI ≥ 22kg/m\^2
• Type 2 diabetes with HbA1c between 6.5% and 10.0%
• Documented symptomatic chronic heart failure (NYHA II-IV)
• Plasma NT-proBNP \> 300pg/ml
• eGFR ≥ 45ml/min/1.73m\^2 (calculated by MDRD)

You may not qualify if:

• Pregnant or nursing (lactating) women
• Type 1 diabetes, monogenic diabetes, diabetes resulting from pancreatic injury, or secondary forms of diabetes
• History of ketoacidosis, lactic acidosis, or hyperosmolar coma
• Symptomatic genital infection or UTI within 4 weeks of screening
• Myocardial infarction, stroke, surgery for heart disease, percutaneous coronary intervention within 3 months of randomization
• Unstable angina within 3 months of screening
• Isolated right HF due to pulmonary disease
• Patients with a mean sitting systolic blood pressure ≤ 100mmHg, at randomization
• History of lower limb amputation
• Diabetic foot ulcer at screening

Sponsors & Collaborators

• Novartis Pharmaceuticals: lead

Study Sites (106)

Novartis Investigative Site

Huntsville, Alabama, 35801, United States

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Novartis Investigative Site

Carmichael, California, 95608, United States

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Novartis Investigative Site

Concord, California, 94520, United States

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Novartis Investigative Site

Long Beach, California, 90813, United States

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Novartis Investigative Site

Northridge, California, 91325, United States

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Novartis Investigative Site

Stockton, California, 95204, United States

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Colorado Springs, Colorado, 80906, United States

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Novartis Investigative Site

Bradenton, Florida, 34209, United States

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Novartis Investigative Site

Clearwater, Florida, 33756, United States

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Novartis Investigative Site

Delray Beach, Florida, 33446, United States

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Novartis Investigative Site

Fort Lauderdale, Florida, 33312, United States

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Novartis Investigative Site

Gurnee, Illinois, 60031, United States

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Bogalusa, Louisiana, 70427, United States

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Novartis Investigative Site

Jackson, Mississippi, 39209, United States

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St Louis, Missouri, 63128, United States

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Omaha, Nebraska, 68114, United States

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Charleston, South Carolina, 29407, United States

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Columbia, South Carolina, 29203, United States

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San Antonio, Texas, 78229, United States

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Novartis Investigative Site

Sugar Land, Texas, 77479, United States

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Tacoma, Washington, 98405, United States

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Novartis Investigative Site

CABA, Buenos Aires, 1407, Argentina

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Novartis Investigative Site

CABA, Buenos Aires, C1056ABJ, Argentina

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Novartis Investigative Site

CABA, Buenos Aires F.D., C1179AAB, Argentina

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Novartis Investigative Site

Buenos Aires, C1120AAC, Argentina

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Graz, A-8036, Austria

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Vienna, 1090, Austria

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Vienna, 1130, Austria

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Novartis Investigative Site

Lennik, Brussels Capital, 1070, Belgium

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Novartis Investigative Site

Aalst, 9300, Belgium

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Novartis Investigative Site

Bonheiden, 2820, Belgium

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Leuven, 3000, Belgium

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Liège, 4000, Belgium

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Sofia, 1233, Bulgaria

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Sofia, 1309, Bulgaria

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Sofia, 1431, Bulgaria

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Sofia, 1709, Bulgaria

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Novartis Investigative Site

London, Ontario, N6A 5A5, Canada

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Toronto, Ontario, M5B 1W8, Canada

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Montreal, Quebec, H4A 3J1, Canada

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Québec, Quebec, G1V 4G2, Canada

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Saint-Jérôme, Quebec, J7Z 5T3, Canada

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Novartis Investigative Site

Sainte-Foy, Quebec, G1V 4G5, Canada

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Novartis Investigative Site

Krapinske Toplice, 49 217, Croatia

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Novartis Investigative Site

Rijeka, 51000, Croatia

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Novartis Investigative Site

Zagreb, 10000, Croatia

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Novartis Investigative Site

Brandýs nad Labem, Czech Republic, 250 01, Czechia

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Novartis Investigative Site

Svitavy, Czech Republic, 568 25, Czechia

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Novartis Investigative Site

Třebíč, Czech Republic, 674 01, Czechia

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Novartis Investigative Site

Fryštát, 73506, Czechia

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Novartis Investigative Site

Kolín, 280 20, Czechia

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Prague, 12808, Czechia

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Novartis Investigative Site

Prague, 158 00, Czechia

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Novartis Investigative Site

Přerov, 751 52, Czechia

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Novartis Investigative Site

Hellerup, 2900, Denmark

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Svendborg, 5700, Denmark

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Novartis Investigative Site

Bad Oeynhausen, 32545, Germany

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Berlin, 10789, Germany

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Novartis Investigative Site

Berlin, 12157, Germany

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Novartis Investigative Site

Berlin, 13347, Germany

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Frankfurt, 60594, Germany

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Halle, 06120, Germany

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Hamburg, 20099, Germany

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Stuttgart, 70378, Germany

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Budapest, HUN, 1145, Hungary

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Budapest, 1134, Hungary

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Szeged, 6720, Hungary

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Szekszárd, 7100, Hungary

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Wilton, Cork, Ireland

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County Limerick, V94 F858, Ireland

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Dublin, Ireland

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Bergamo, BG, 24127, Italy

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Milan, MI, 20132, Italy

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San Donato Milanese, MI, 20097, Italy

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Milan, 20149, Italy

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Rimini, 47923, Italy

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Durango, 34000, Mexico

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Alkmaar, 1815 JD, Netherlands

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Groningen, 9713 GZ, Netherlands

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Utrecht, 3584 CX, Netherlands

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Venlo, 5912 BL, Netherlands

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Novartis Investigative Site

Loerenskog, NO 1478, Norway

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Oslo, 0372, Norway

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Trondheim, 7006, Norway

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Warsaw, 00-874, Poland

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Wroclaw, 51-314, Poland

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Novartis Investigative Site

Ponce, 00717, Puerto Rico

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Singapore, 169609, Singapore

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Novartis Investigative Site

Bloemfontein, Free State, 9301, South Africa

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Novartis Investigative Site

Paarl, Western Cape, 7626, South Africa

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Novartis Investigative Site

Worcester, 6850, South Africa

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Novartis Investigative Site

Wŏnju, Gangwon-do, 26426, South Korea

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Novartis Investigative Site

Bundang Gu, Gyeonggi-do, 13620, South Korea

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Novartis Investigative Site

Cheongju-si, North Chungcheong, 28644, South Korea

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Novartis Investigative Site

Seoul, 03080, South Korea

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Novartis Investigative Site

Seville, Andalusia, 41014, Spain

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Novartis Investigative Site

Villamartín, Cadiz, 11650, Spain

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Novartis Investigative Site

Cáceres, Extremadura, 10003, Spain

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Novartis Investigative Site

Valencia, Valencia, 46010, Spain

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Novartis Investigative Site

Changhua, 50006, Taiwan

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Novartis Investigative Site

Taichung, 40447, Taiwan

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Novartis Investigative Site

Taipei, 11217, Taiwan

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Novartis Investigative Site

Chelmsford, Essex, CM1 7ET, United Kingdom

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Novartis Investigative Site

London, GBR, EC1M 6BQ, United Kingdom

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Novartis Investigative Site

Sunderland, Tyne and Wear, SR4 7TP, United Kingdom

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Novartis Investigative Site

Birmingham, B15 2TH, United Kingdom

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MeSH Terms

Conditions

Diabetes Mellitus; Heart Failure; Obesity; Diabetes Mellitus, Type 2; Hypertension; Renal Insufficiency; Hyperglycemia

Interventions

licogliflozin; empagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Heart Diseases; Cardiovascular Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Vascular Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases

Limitations and Caveats

Due to early discontinuation of the study, the analysis of efficacy was done on the available data (mostly for Epoch 3 (double-blind period 1) only). Because of the small sample sizes the interpretation of the results remained limited.

Results Point of Contact

• Title: Study Director
• Organization: Novartis Pharmaceuticals

Novartis.email@novartis.com

862-778-8300

Study Officials

• Novartis Pharmaceuticals

  Novartis Pharmaceuticals

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 8, 2017
• First Posted: May 15, 2017
• Study Start: July 25, 2017
• Primary Completion: June 6, 2018
• Study Completion: June 6, 2018
• Last Updated: August 28, 2019
• Results First Posted: August 28, 2019

Record last verified: 2019-08

Locations

NO (3); NL (4); PL (2); PR (1); SG (1); ZA (3); ES (4); ME (1); KR (4); CR (3); CZ (8); DK (2); TW (3); AU (3); BU (4); GB (4); IE (3); BE (5); IT (5); HU (4); AR (4); US (21); DE (8); CA (6)