Clinical trial NCT02827708: Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment
Official title: Efficacy and Safety of Oral Semaglutide Versus Placebo in Subjects With Type 2 Diabetes and Moderate Renal Impairment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Diabetes
Diabetes Mellitus, Type 2
Lead sponsor: Novo Nordisk A/S
Sponsor class: INDUSTRY
First posted: 2016-07-11
Enrollment: 324
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This trial is conducted globally. The aim of this trial is to investigate efficacy and safety of oral semaglutide versus placebo in subjects with type 2 diabetes and moderate renal impairment.


Eligibility criteria: Inclusion Criteria:

* Informed consent obtained before any trial-related activities. Trial-related activities are any procedures that are carried out as part of the trial, including activities to determine suitability for the trial
* Male or female, age above or equal to 18 years at the time of signing informed consent
* Diagnosed with type 2 diabetes mellitus for at least 90 days prior to day of screening
* HbA1c (glycosylated haemoglobin) of 7.0-9.5% (53-80 mmol/mol) (both inclusive)
* Moderate renal impairment defined as estimated glomerular filtration rate of 30-59 mL/min/1.73 m\^2 as per Chronic Kidney Disease Epidemiology Collaboration formula
* Stable daily dose(s) within 90 days prior to the day of screening of any of the following treatment regimens:
* 1-2 of the following oral anti-diabetic drugs:
* Metformin equal or above 1500 mg or maximum tolerated dose documented in the subject medical record),
* Sulfonylurea (equal or above half of the maximum approved dose according to local label or maximum tolerated dose as documented in subject medical record)
* Basal insulin alone (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin) or
* Metformin (equal or above 1500 mg or maximum tolerated dose documented in the subject medical record) in combination with basal insulin (20% change in total daily dose of insulin glargine, insulin detemir, insulin degludec or NPH insulin)

Exclusion Criteria:

* Female who is pregnant, breast-feeding or intends to become pregnant or is of child-bearing potential and not using an adequate contraceptive method (adequate contraceptive measure as required by local regulation or practice). For certain specific countries: Additional specific requirements apply
* Any disorder, which in the investigator's opinion might jeopardise subject's safety or compliance with the protocol
* Family or personal history of Multiple Endocrine Neoplasia Type 2 or Medullary Thyroid Carcinoma
* History of pancreatitis (acute or chronic)
* History of major surgical procedures involving the stomach potentially affecting absorption of trial product (e.g. subtotal and total gastrectomy, sleeve gastrectomy, gastric bypass surgery)
* Any of the following: myocardial infarction, stroke or hospitalisation for unstable angina or transient ischaemic attack within the past 180 days prior to the day of screening and randomisation
* Subjects presently classified as being in New York Heart Association Class IV
* Planned coronary, carotid or peripheral artery revascularisation known on the day of screening
* Subjects with alanine aminotransferase above 2.5 x upper normal limit
* Rapidly progressing renal disease (e.g. such as acute glomerulonephritis) as judged by the investigator or known nephrotic albuminuria (above 2200 mg/24 hours or above 2200 mg/g)
* Use of systemic immunosuppressive treatment within 90 days prior to screening
* Treatment with any medication for the indication of diabetes or obesity other than stated in the inclusion criteria in a period of 90 days before the day of screening. An exception is short-term insulin treatment for acute illness for a total of below or equal to 14 days
* Known hypoglycaemic unawareness and/or recurrent severe hypoglycaemic episodes as judged by the investigator
* Proliferative retinopathy or maculopathy requiring acute treatment. Verified by fundus photography or dilated fundoscopy performed within 90 days prior to randomisation
* History or presence of malignant neoplasms within the last 5 years (except basal and squamous cell skin cancer and carcinoma in situ)

Primary outcomes:
measure: Change in HbA1c
timeFrame: Week 0, week 26
Secondary outcomes:
measure: Change in Body Weight (kg)
timeFrame: Week 0, week 26
measure: Change in FPG
timeFrame: Week 0, week 26
measure: Change in Body Weight (%)
timeFrame: Week 0, week 26
measure: Change in BMI
timeFrame: Week 0, week 26
measure: Change in Waist Circumference
timeFrame: Week 0, week 26
measure: Participants Who Achieve HbA1c <7.0% (53 mmol/Mol), ADA Target (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieve HbA1c ≤6.5% (48 mmol/Mol), AACE Target (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieve Weight Loss ≥5% (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieve Weight Loss ≥10% (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieve HbA1c <7.0 % (53 mmol/Mol) Without Hypoglycaemia (Severe or BG Confirmed Symptomatic Hypoglycaemia) and no Weight Gain (Yes/no)
timeFrame: Week 26
measure: Participants Who Achieve HbA1c Reduction ≥1% (10.9 mmol/Mol) and Weight Loss ≥3% (Yes/no)
timeFrame: Week 26
measure: Change in Total Cholesterol (Ratio to Baseline)
timeFrame: Week 0, week 26
measure: Change in LDL Cholesterol (Ratio to Baseline)
timeFrame: Week 0, week 26
measure: Change in HDL Cholesterol (Ratio to Baseline)
timeFrame: Week 0, week 26
measure: Change in Triglycerides (Ratio to Baseline)
timeFrame: Week 0, week 26
measure: Change in CRP (Ratio to Baseline)
timeFrame: Week 0, week 26
measure: Time to Additional Anti-diabetic Medication
timeFrame: Weeks 0-26
measure: Time to Rescue Medication
timeFrame: Weeks 0-26
measure: Number of TEAEs
timeFrame: Weeks 0-31
measure: Number of Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes
timeFrame: Weeks 0-31
measure: Participants With Treatment-emergent Severe or BG-confirmed Symptomatic Hypoglycaemic Episodes (Yes/no)
timeFrame: Weeks 0-31
measure: Change in Amylase (Ratio to Baseline)
timeFrame: Week 0, week 26
measure: Change in Lipase (Ratio to Baseline)
timeFrame: Week 0, week 26
measure: Change in Pulse Rate
timeFrame: Week 0, week 26
measure: Change in Blood Pressure (Systolic and Diastolic Blood Pressure)
timeFrame: Week 0, week 26
measure: Change in Urinary Albumin to Creatinine Ratio (Ratio to Baseline)
timeFrame: Week 0, week 26
measure: Change in ECG
timeFrame: Week 0, week 26
measure: Change in Physical Examination
timeFrame: Week -2, week 26
measure: Change in Eye Examination
timeFrame: Week -2, week 26
measure: Occurrence of Anti-semaglutide Binding Antibodies (Yes/no)
timeFrame: Weeks 0-31
measure: Occurrence of Anti-semaglutide Neutralising Antibodies (Yes/no)
timeFrame: Weeks 0-31
measure: Occurrence of Anti-semaglutide Binding Antibodies Cross Reacting With Native GLP-1 (Yes/no)
timeFrame: Weeks 0-31
measure: Occurrence of Anti-semaglutide Neutralising Antibodies Cross Reacting With Native GLP-1 (Yes/no)
timeFrame: Weeks 0-31
measure: Anti-semaglutide Binding Antibody Levels
timeFrame: Weeks 0-31
measure: Semaglutide Plasma Concentrations for Population PK Analyses
timeFrame: Weeks 0-26
measure: SNAC Plasma Concentrations
timeFrame: Weeks 0-26
measure: Change in Short Form Health Survey Version 2.0 (SF-36v2™, Acute Version) Health Survey: Scores From the 8 Domains and Summaries of the Physical Component Score (PCS) and the Mental Component Score (MCS)
timeFrame: Week 0, week 26
measure: Change in DTSQs: Individual Items and Treatment Satisfaction Score (6 of the 8 Items Summed)
timeFrame: Week 0, week 26
measure: Change in Urinalysis
timeFrame: Week -2, week 26
Other outcomes:
Locations:
city: Tuscumbia
country: United States
facility: Novo Nordisk Investigational Site
state: Alabama
city: Bermuda Dunes
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Concord
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Costa Mesa
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Fresno
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: La Jolla
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: San Ramon
country: United States
facility: Novo Nordisk Investigational Site
state: California
city: Danbury
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Norwalk
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Waterbury
country: United States
facility: Novo Nordisk Investigational Site
state: Connecticut
city: Clearwater
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Cooper City
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Jacksonville
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Miami Lakes
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: New Port Richey
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Orlando
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Palm Harbor
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Pembroke Pines
country: United States
facility: Novo Nordisk Investigational Site
state: Florida
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Atlanta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Lawrenceville
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Marietta
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Roswell
country: United States
facility: Novo Nordisk Investigational Site
state: Georgia
city: Gurnee
country: United States
facility: Novo Nordisk Investigational Site
state: Illinois
city: Avon
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Franklin
country: United States
facility: Novo Nordisk Investigational Site
state: Indiana
city: Slidell
country: United States
facility: Novo Nordisk Investigational Site
state: Louisiana
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Baltimore
country: United States
facility: Novo Nordisk Investigational Site
state: Maryland
city: Buckley
country: United States
facility: Novo Nordisk Investigational Site
state: Michigan
city: Omaha
country: United States
facility: Novo Nordisk Investigational Site
state: Nebraska
city: Lebanon
country: United States
facility: Novo Nordisk Investigational Site
state: New Hampshire
city: Nashua
country: United States
facility: Novo Nordisk Investigational Site
state: New Hampshire
city: Teaneck
country: United States
facility: Novo Nordisk Investigational Site
state: New Jersey
city: Albany
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: New Hyde Park
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Northport
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: West Seneca
country: United States
facility: Novo Nordisk Investigational Site
state: New York
city: Asheboro
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Whiteville
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Wilmington
country: United States
facility: Novo Nordisk Investigational Site
state: North Carolina
city: Fargo
country: United States
facility: Novo Nordisk Investigational Site
state: North Dakota
city: Dayton
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Delaware
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Franklin
country: United States
facility: Novo Nordisk Investigational Site
state: Ohio
city: Norman
country: United States
facility: Novo Nordisk Investigational Site
state: Oklahoma
city: Murrells Inlet
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Myrtle Beach
country: United States
facility: Novo Nordisk Investigational Site
state: South Carolina
city: Kingsport
country: United States
facility: Novo Nordisk Investigational Site
state: Tennessee
city: Amarillo
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Dallas
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Houston
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Midland
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: San Antonio
country: United States
facility: Novo Nordisk Investigational Site
state: Texas
city: Richmond
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Winchester
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Winchester
country: United States
facility: Novo Nordisk Investigational Site
state: Virginia
city: Olympia
country: United States
facility: Novo Nordisk Investigational Site
state: Washington
city: Aalborg
country: Denmark
facility: Novo Nordisk Investigational Site
city: Gentofte
country: Denmark
facility: Novo Nordisk Investigational Site
city: Hvidovre
country: Denmark
facility: Novo Nordisk Investigational Site
city: København S
country: Denmark
facility: Novo Nordisk Investigational Site
city: Køge
country: Denmark
facility: Novo Nordisk Investigational Site
city: Svendborg
country: Denmark
facility: Novo Nordisk Investigational Site
city: Århus C
country: Denmark
facility: Novo Nordisk Investigational Site
city: Espoo
country: Finland
facility: Novo Nordisk Investigational Site
city: Helsinki
country: Finland
facility: Novo Nordisk Investigational Site
city: Kerava
country: Finland
facility: Novo Nordisk Investigational Site
city: Kuopio
country: Finland
facility: Novo Nordisk Investigational Site
city: Oulu
country: Finland
facility: Novo Nordisk Investigational Site
city: Turku
country: Finland
facility: Novo Nordisk Investigational Site
city: Ähtäri
country: Finland
facility: Novo Nordisk Investigational Site
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Haifa
country: Israel
facility: Novo Nordisk Investigational Site
city: Jerusalem
country: Israel
facility: Novo Nordisk Investigational Site
city: Kfar Saba
country: Israel
facility: Novo Nordisk Investigational Site
city: Rehovot
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel Hashomer
country: Israel
facility: Novo Nordisk Investigational Site
city: Tel-Aviv
country: Israel
facility: Novo Nordisk Investigational Site
city: Poznan
country: Poland
facility: Novo Nordisk Investigational Site
city: Zabrze
country: Poland
facility: Novo Nordisk Investigational Site
city: Barnaul
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Barnaul
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Belgorod
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Chelyabinsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Dzerzhinskiy
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Kazan
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Moscow
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Penza
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saint-Petersburg
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Saratov
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Tomsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Ulianovsk
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Volgograd
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Voronezh
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Yaroslavl
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Yoshkar-Ola
country: Russian Federation
facility: Novo Nordisk Investigational Site
city: Göteborg
country: Sweden
facility: Novo Nordisk Investigational Site
city: Lund
country: Sweden
facility: Novo Nordisk Investigational Site
city: Skövde
country: Sweden
facility: Novo Nordisk Investigational Site
city: Uppsala
country: Sweden
facility: Novo Nordisk Investigational Site
city: Vindeln
country: Sweden
facility: Novo Nordisk Investigational Site
city: Örebro
country: Sweden
facility: Novo Nordisk Investigational Site
city: Bexhill-on-Sea
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Doncaster
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Edinburgh
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Glasgow
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Hull
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Milton Keynes
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Rothwell
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Sheffield
country: United Kingdom
facility: Novo Nordisk Investigational Site
city: Wellingborough
country: United Kingdom
facility: Novo Nordisk Investigational Site
Study officials:
References:
citation: Mosenzon O, Blicher TM, Rosenlund S, Eriksson JW, Heller S, Hels OH, Pratley R, Sathyapalan T, Desouza C; PIONEER 5 Investigators. Efficacy and safety of oral semaglutide in patients with type 2 diabetes and moderate renal impairment (PIONEER 5): a placebo-controlled, randomised, phase 3a trial. Lancet Diabetes Endocrinol. 2019 Jul;7(7):515-527. doi: 10.1016/S2213-8587(19)30192-5. Epub 2019 Jun 9.
citation: Mosenzon O, Capehorn MS, De Remigis A, Rasmussen S, Weimers P, Rosenstock J. Impact of semaglutide on high-sensitivity C-reactive protein: exploratory patient-level analyses of SUSTAIN and PIONEER randomized clinical trials. Cardiovasc Diabetol. 2022 Sep 2;21(1):172. doi: 10.1186/s12933-022-01585-7.
citation: Pratley RE, Crowley MJ, Gislum M, Hertz CL, Jensen TB, Khunti K, Mosenzon O, Buse JB. Oral Semaglutide Reduces HbA1c and Body Weight in Patients with Type 2 Diabetes Regardless of Background Glucose-Lowering Medication: PIONEER Subgroup Analyses. Diabetes Ther. 2021 Apr;12(4):1099-1116. doi: 10.1007/s13300-020-00994-9. Epub 2021 Mar 4.
citation: Husain M, Bain SC, Holst AG, Mark T, Rasmussen S, Lingvay I. Effects of semaglutide on risk of cardiovascular events across a continuum of cardiovascular risk: combined post hoc analysis of the SUSTAIN and PIONEER trials. Cardiovasc Diabetol. 2020 Sep 30;19(1):156. doi: 10.1186/s12933-020-01106-4.
citation: Thethi TK, Pratley R, Meier JJ. Efficacy, safety and cardiovascular outcomes of once-daily oral semaglutide in patients with type 2 diabetes: The PIONEER programme. Diabetes Obes Metab. 2020 Aug;22(8):1263-1277. doi: 10.1111/dom.14054. Epub 2020 May 13.
citation: Husain M, Bain SC, Jeppesen OK, Lingvay I, Sorrig R, Treppendahl MB, Vilsboll T. Semaglutide (SUSTAIN and PIONEER) reduces cardiovascular events in type 2 diabetes across varying cardiovascular risk. Diabetes Obes Metab. 2020 Mar;22(3):442-451. doi: 10.1111/dom.13955. Epub 2020 Feb 5.