This is an inpatient treatment, double-blind, randomized, 3-way crossover study in T1DM subjects using insulin pump therapy.
Subjects will be randomized to one of 6 treatment sequences. The randomized study drug will be administered once daily for 7 days throughout each of 3 treatment periods. Each subject will attend an in-house baseline period, the NoTreatment period, and 3 in-house treatment periods, The Active Periods, where the same assessments will be performed. At each of the in-house periods, a MMTT will be carried out on the sixth day of dosing and an insulin withdrawal test will be carried out on the seventh day of dosing. Postprandial glycemic excursion after a MMTT will be evaluated one day prior to an insulin withdrawal test. An insulin pumps with different modes (such as open loop/closed loop) the mode used at screening will be the mode used throughout the study. Unblinded continuous glucose monitoring (CGM) will be initiated at the start of the 7-day Baseline Period (Day -7) and discontinued at End of Treatment (Day 34).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
19
YG1699 is a novel investigational dual inhibitor of sodium-dependent glucose cotransporters, SGLT1 and SGLT2, indicated as an adjunct to diet and exercise to improve glycemic control and weight loss in adults with T2DM. A subsequent indication will be developed for YG1699 to improve glycemic control in adults with T1DM. The proposed dosage form is a yellow, film-coated tablet for oral administration. The proposed tablet strengths for the current clinical research are 5 mg and 25 mg. The tablets are packaged in high-density polyethylene (HDPE) bottles with HDPE caps and desiccant inserters. Each HDPE bottle contains 30 tablets of drug product. The study drug YG1699 is manufactured by Youngene Therapeutics Inc., Ltd., China.
Farxiga® is a sodium-glucose cotransporter 2 (SGLT2) inhibitor. Faxiga® is available as a film-coated tablet for oral administration containing the equivalent of 5 mg dapagliflozin as dapagliflozin propanediol and the following inactive ingredients: microcrystalline cellulose, anhydrous lactose, crospovidone, silicon dioxide, and magnesium stearate. In addition, the film coating contains the following inactive ingredients: polyvinyl alcohol, titanium dioxide, polyethylene glycol, talc, and yellow iron oxide.
ProSciento, Inc
Chula Vista, California, United States
Concentration-time curve in plasma glucose (AUC(0-120min) )
To demonstrate that either dose of YG1699 produces a lower area under the concentration-time curve in plasma glucose (AUC(0-120min) ) \[mg/dL\*ml\] expressed as percent of No Treatment mean versus Dapagliflozin after a standardized Mixed Meal Tolerance Test (MMTT), performed on the 6th day of treatment.
Time frame: 6th day of treatment
Objectives for MMTT
* To evaluate the change from the No Treatment Period versus the Active Treatment Periods in plasma glucose after the MMTT, performed on the 6th day of treatment, at 2-hour postprandial (120 minutes) of YG1699 doses versus Dapagliflozin (This endpoint may become primary endpoint after interim analysis) * To evaluate the change from the No Treatment Period versus the Active Treatment Periods in urinary glucose excretion (UGE) after the MMTT on the 6th day of treatment, (UGE 0-180 minutes) of YG1699 doses versus Dapagliflozin * To evaluate the change from the No Treatment Period versus the Active Treatment Periods in plasma glucose after the MMTT, performed on the 6th day of treatment, during 3-hour postprandial (180 minutes) at individual time points, and maximum plasma glucose of YG1699 doses versus Dapagliflozin
Time frame: 6th day of treatment
Objectives for Insulin Withdrawal
• To evaluate the increment and ratio of changes from the No Treatment Period versus the Active Treatment Periods during insulin withdrawal performed on the 7th day of treatment, in: * Treatment Ratios (95% CI) of the following: Serum beta-hydroxybutyrate (BOHB) , plasma glucagon , plasma glucose , plasma free fatty acids (FFA) * Duration of insulin withdrawal
Time frame: 7th day of treatment
Objectives for Insulin Requirements
To evaluate the change from the No Treatment Period versus the Active Treatment Periods in basal, bolus and total daily insulin dose requirements
Time frame: over 3 days prior to the MMTT
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