Does Dapagliflozin Provide Additional Health Benefits To... | NCT03180489

NCT03180489

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

Large Document Module

Derived Section

Miscellaneous Info Module

Status Module

Name	Class
AstraZeneca	INDUSTRY

Description Module

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
Dapagliflozin with dietary counseling	Experimental	Daily oral administration of dapagliflozin tablet with dietary counseling to promote weight loss.	Drug: Dapagliflozin Tablet
Placebo with dietary counseling	Placebo Comparator	Daily oral administration of placebo tablet with dietary counseling to promote weight loss.	Drug: Placebo Tablet

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Dapagliflozin Tablet	Drug	Daily oral administration of dapagliflozin with dietary counseling to promote weight loss. Dapagliflozin 5 mg tablet will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Change From Baseline in Insulin Sensitivity at Week 12 Via Oral Glucose Tolerance Test	Insulin sensitivity was estimated by measuring circulating insulin concentrations after a 12 hour fast and after ingesting 75 g of glucose. Insulin was measured 0, 30, 60, 90 and 120 minutes after glucose ingestion. Time point 0 minutes is reported below.	Baseline, 12 weeks
Change From Baseline in Blood Pressure at Week 12	Blood pressure was measured with an automatic machine at baseline. Numbers are reported as systolic/diastolic	Baseline, 12 weeks
Change From Baseline in Perception of Satiety at Week 12	Participants answered a satiety questionnaire before liquid meal primer, immediately post liquid meal primer, 60 minutes post liquid primer, immediately post breakfast buffet, 60 minutes, 120 minutes and 180 minutes post breakfast buffet. Responses how full do you feel right now? for 60 minutes post liquid meal primer ingestion are reported below. This was determined by using a visual analog scale. The left side of the analog scale represents a null answer (e.g. How full do you feel right now)? Answer 0: Not full at all. The right side of the line represented the strongest answer in the opposite direction (e.g. How full to you feel right now)? Answer 100: Extremely full. The length of the line is 100 mm, thus the scale ranges for all answers were 0-100. All values are reported as values between 0 and 100. If the answers to the fullness questions increased, this represented a decreased desire to eat.	Baseline, 12 weeks
Change From Baseline in Perception of Hunger at Week 12	Participants answered a hunger questionnaire before liquid meal primer, immediately post liquid meal primer, 60 minutes post liquid primer, immediately post breakfast buffet, 60 minutes, 120 minutes and 180 minutes post breakfast buffet. Responses to how hungry do you feel right now? for 60 minutes post liquid meal primer ingestion are reported below. This was determined by using a visual analog scale. The left side of the analog scale represents a null answer (e.g. How hungry do you feel right now? Answer 0: Not hungry at all. The right side of the line represented the strongest answer in the opposite direction (e.g. How full to you feel right now)? Answer 100: Extremely hungry. The length of the line is 100 mm, thus the scale ranges for all answers were 0-100. All values are reported as values between 0 and 100. If the answers to the fullness questions increased, this represented an increased desire to eat.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Provision of informed consent prior to any study specific procedures.
Aged 18-65 years.
No known Type 2 Diabetes
Body mass index greater than or equal to 27.5 kg/m^2
Limited exercise participation (maximum of 3/week regularly scheduled activity sessions of < 30 minutes during the previous month).
Completion of a screening visit consisting of medical history, physical examination, and 12-lead electrocardiogram and blood pressure assessment at rest and during incremental exercise to volitional exhaustion (Note: Subjects with abnormal screening values may be eligible if the results are not clinically significant, as judged by the investigator or medical monitor)
Agree to abide by the study schedule and dietary restrictions and to return for the required assessments
Women of childbearing potential must have negative pregnancy test and be using acceptable contraception

Exclusion Criteria:

Evidence of clinically significant cardiovascular, respiratory, renal, hepatic, pulmonary, gastrointestinal, haematological, neurological, psychiatric, or other disease that may interfere with the objectives of the study or the safety of the subject, as judged by the investigator in agreement with the sponsor or medical monitor, have been hospitalized in the past 2 years as a result of these conditions, or are receiving pharmacological treatment for these conditions.
Use of prescription drugs (see exceptions listed below) or herbal preparations in the 2 weeks before study commencement. Prior use of medication or herbal preparations in the 4 weeks before study commencement that are intended for weight-loss and/or sold/marketed as weight-loss products or may alter metabolism. Permitted Prescription Drugs: Birth Control, Less than a 7 day short course of antibiotics. Note: Rifampicin is not permitted. Other medicines, such as those for gastroesophageal reflux disease, depression, and Over The Counter analgesics and allergy medications,may be allowed, but will be approved on a case-by-case basis.
Is currently enrolled in another clinical study for another investigational drug or has taken any other investigational drug within 30 days before the screening visit.
Habitual and/or recent use (within 2 years) of tobacco.
Being considered unsuitable for participation in this trial for any reason, as judged by the investigator or medical monitor.
History of serious hypersensitivity reaction to Dapagliflozin.
Severe renal impairment, end-stage renal disease, or dialysis.
Pregnant or breastfeeding individual.
Severe hepatic insufficiency and/or significant abnormal liver function defined as aspartate aminotransferase (AST) >3x upper limit of normal and/or alanine aminotransferase (ALT) >3x upper limit of normal.
Total bilirubin >2.0 mg/dL (34.2 umol/L).
Positive serologic evidence of current infectious liver disease including Hepatitis B viral antibody immunoglobulin M, Hepatitis B surface antigen and Hepatitis C virus antibody.
Estimated Glomerular Filtration Rate <60 mL/min/1.73 m^2 (calculated by Cockcroft-Gault formula).
History of bladder cancer.
Recent cardiovascular events in a patient, including any of the following: acute coronary syndrome within 2 months prior to enrolment; hospitalization for unstable angina or acute myocardial infarction within 2 months prior to enrolment; acute stroke or trans-ischemic attack within two months prior to enrolment; less than two months post coronary artery revascularization; congestive heart failure defined as New York Heart Association class IV, unstable or acute congestive heart failure. Note: eligible patients with congestive heart failure, especially those who are on diuretic therapy, should have careful monitoring of their volume status throughout the study.
Blood pressure at enrolment: Systolic blood pressure ≥160 mmHg and/or diastolic blood pressure ≥100 mmHg.
Blood pressure at randomization: Systolic blood pressure ≥165 mmHg and/or diastolic blood pressure ≥100 mmHg
Individuals who, in the judgment of the medical monitor, may be at risk for dehydration.
Individuals with a history of fragility fracture, or bone mineral density values reflective of risk for fracture (DEXA Z-score \

Name	Affiliation	Role
Christopher Bell, Ph.D.	Colorado State University	Principal Investigator
Christopher Melby, Dr.P.H.	Colorado State University	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Colorado State University, Dept. of Health and Exercise Science		Fort Collins	Colorado	80523-1582	United States

Arm/Group Information

ID	Title	Description
FG000	Dapagliflozin With Dietary Counseling	Daily oral administration of dapagliflozin tablet with dietary counseling to promote weight loss. Dapagliflozin Tablet: Daily oral administration of dapagliflozin with dietary counseling to promote weight loss. Dapagliflozin 5 mg tablet will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.
FG001	Placebo With Dietary Counseling	Daily oral administration of placebo tablet with dietary counseling to promote weight loss. Placebo Tablet: Daily administration of placebo tablet with dietary counseling to promote weight loss. Matching placebo for dapagliflozin 5 mg tablet will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.

Baseline Characteristics Module

Arm/Group Information

ID	Title	Description
BG000	Dapagliflozin With Dietary Counseling	Daily oral administration of dapagliflozin tablet with dietary counseling to promote weight loss. Dapagliflozin Tablet: Daily oral administration of dapagliflozin with dietary counseling to promote weight loss. Dapagliflozin 5 mg tablet will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.

Units	Counts
Participants	BG000

Baseline Measures

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Change From Baseline in Insulin Sensitivity at Week 12 Via Oral Glucose Tolerance Test

Insulin sensitivity was estimated by measuring circulating insulin concentrations after a 12 hour fast and after ingesting 75 g of glucose. Insulin was measured 0, 30, 60, 90 and 120 minutes after glucose ingestion. Time point 0 minutes is reported below.

Posted

Mean

Standard Deviation

mU/L

Baseline, 12 weeks

ID	Title	Description
OG000	Dapagliflozin With Dietary Counseling	Daily oral administration of dapagliflozin tablet with dietary counseling to promote weight loss. Dapagliflozin Tablet: Daily oral administration of dapagliflozin with dietary counseling to promote weight loss. Dapagliflozin 5 mg tablet will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Dapagliflozin With Dietary Counseling	Daily oral administration of dapagliflozin tablet with dietary counseling to promote weight loss. Dapagliflozin Tablet: Daily oral administration of dapagliflozin with dietary counseling to promote weight loss. Dapagliflozin 5 mg tablet will begin as one tablet per day for the first 14-days. In the absence of complications, side effects, or unfavorable reactions, the dose will then increase to two tablets for the remainder of the study.

ID	Term
D001836	Body Weight Changes
D001835	Body Weight
D012816	Signs and Symptoms
D013568	Pathological Conditions, Signs and Symptoms