A Comparison of Postprandial Glucose After a MMTT, and the Metabolic Effects of Insulin Withdrawal in a Crossover Study in Subjects With Type 1 Diabetes

NCT04956263 | Completed Phase 2 FDA Drug

• 1 other identifier: YG1699-201
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

This is an inpatient treatment, double-blind, randomized, 3-way crossover study in T1DM subjects using insulin pump therapy.

Conditions

Diabetes; Diabetes Mellitus, Type 1; Type1diabetes; Diabetes Mellitus

Keywords

Mixed Meal Tolerance Test; Insulin Withdrawal

Outcome Measures

Primary Outcomes (1)

• 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.

  6th day of treatment

Secondary Outcomes (3)

• Objectives for MMTT

  6th day of treatment

• Objectives for Insulin Withdrawal

  7th day of treatment

• Objectives for Insulin Requirements

  over 3 days prior to the MMTT

Study Arms (3)

Treatment A

EXPERIMENTAL

YG1699 10 mg

Drug: YG1699

Treatment B

EXPERIMENTAL

YG1699 25 mg

Drug: YG1699

Treatment C

ACTIVE COMPARATOR

Dapagliflozin 10 mg

Drug: Dapagliflozin

Interventions

YG1699 DRUG

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.

Treatment A; Treatment B

Dapagliflozin DRUG

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.

Also known as: Farxiga

Treatment C

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Subjects ≥ 18 to ≤ 60 years of age at the time of signing the informed consent.
• Subjects diagnosed with T1DM for ≥ 12 months.
• Subjects who are currently using an approved insulin pump, with a stable basal insulin dose. Stable is defined as \< 20% change of dose during the last 2 weeks prior to Screening.
• HbA1c \< 9.5%.
• C-peptide after carbohydrate ingestion of \< 0.3 nmol/L, with simultaneous plasma glucose \> 90 mg/dL. (If necessary, subjects may consume carbohydrates to raise blood glucose over 90 mg/dL as measured by YSI prior to drawing blood for C-peptide. This may be repeated as needed to ensure C-peptide is assessed when plasma glucose concentration is \> 90 mg/dL).
• Fasting BOHB ≤ 0.6 mmol/L.
• Body mass index (BMI) within the range ≥ 18.5 to ≤ 27.0 kg/m2.
• Female subjects must be non-pregnant and non-lactating.
• Females of childbearing potential must use highly effective contraceptive methods, stable at least 2 months prior to the screening. Male subjects must be surgically sterile, abstinent or if engaged in sexual relations of childbearing potential, the subject and his partner must be using acceptable methods of contraception.
• Capable of giving signed informed consent and willing to follow study procedures and commitment to the study duration

You may not qualify if:

• Subject has a diagnosis of type 2 diabetes (T2DM).
• Subject who has acute proliferative retinopathy or maculopathy, requiring acute treatment within 3 months of Screening.
• Subject who has ≥ 3 Level 2 or ≥ 1 Level 3 hypoglycemic events, or hypoglycemic unawareness, or had a severe hypoglycemic event (Level 3) within 1 month prior to Screening.
• Subject who has had DKA or nonketotic hyperosmolar state within 1 month of Screening, OR ≥ 2 events of DKA or nonketotic hyperosmolar state within 6 months of Screening.
• Subject with uncontrolled hypertension, defined as persistent blood pressure (BP) systolic or diastolic \> 150/90 mmHg, or hypotension, defined as BP \< 90/60 mmHg. (Subjects BP may be re-checked per site SOP)
• Subject with any clinically significant active disease of the gastrointestinal system (peptic ulcers, severe GERD, gastroparesis, any malabsorption/motility disorders, or chronic constipation). severe gastroparesis, and/or severe neuropathy, especially autonomic neuropathy, as judged by the Investigator.
• Subject with history of heart disease, defined as symptomatic heart failure (New York Heart Association class III or IV), myocardial infarction, coronary artery bypass graft surgery, or angioplasty, unstable angina requiring medication, transient ischemic attack, cerebral infarct, or cerebral hemorrhage.
• Subject with presence of clinically significant ECG findings (eg, QTcF \> 450 msec for males, QTcF \> 470 msec for females, left bundle branch block \[LBBB\],cardiac arrythmia) at Screening that, in the opinion of the Investigator, may interfere with any aspect of study conduct or interpretation of results, or may present a safety issue to that particular subject.
• Subject with history of renal disease or abnormal kidney function tests at Screening (eGFR \< 60 mL/min/1.73m2 as estimated using the CKD-EPI Creatinine equation).
• History of hereditary glucose-galactose malabsorption or primary renal glucosuria
• Subjects with a thyroid disease, not adequately controlled. (Subjects with TSH outside of reference range due to incorrect treatment may be re-screened and included after successful treatment correction.)
• Subject with a history of significant liver disease, transaminases (AST, ALT) ≥ 2 x upper limit normal (ULN), or total bilirubin \>1.5x ULN. (Laboratory results may be re-checked once on a separate day per Investigator discretion)
• Subject shows evidence of significant active neuropsychiatric disease, or chronic seizures, or major neurological disorders. Subjects that are stable and controlled by stable doses of selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), antipsychotics and lithium for ≥ 3 months prior to screening may be allowed based on the judgement of the investigator.
• Subject with a history of neoplastic disease within the past 5 years, except for adequately treated non-melanomatous skin carcinoma or other malignancies which have been successfully treated ≥10 years prior to screening.
• Subject with a previous surgical treatment for obesity (bariatric surgery, gastric banding, etc.) or any other gastrointestinal surgery that may induce malabsorption, history of bowel resection \> 20 cm, or any GI procedure for weight loss (including LAP-BAND®).

Sponsors & Collaborators

• Youngene Therapeutics Inc., Ltd.: lead
• ProSciento, Inc.: collaborator

Study Sites (1)

ProSciento, Inc

Chula Vista, California, 91911, United States

Location

Related Publications (1)

• Lapuerta P, Urbina S, He J, Wittle A, Li C, Li T, Wang H, Hompesch M. A Randomized Crossover Trial of Mixed Meal Tolerance Test Response in People with Type 1 Diabetes on Insulin Pump Therapy and YG1699 or Dapagliflozin. Clin Pharmacol Ther. 2024 Jun;115(6):1383-1390. doi: 10.1002/cpt.3225. Epub 2024 Mar 8.

  PMID: 38456487 DERIVED

MeSH Terms

Conditions

Diabetes Mellitus; Diabetes Mellitus, Type 1

Interventions

dapagliflozin

Condition Hierarchy (Ancestors)

Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Endocrine System Diseases; Autoimmune Diseases; Immune System Diseases

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Double-blinded, randomized
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: During the No Treatment Period prior to the baseline MMTT performed on Day -2, subjects will be randomized 1:1:1:1:1:1 to one of six Treatment Sequences A/B/C, A/C/B, B/C/A, B/A/C, C/B/A or C/A/B: * Treatment A is YG1699 10 mg * Treatment B is YG1699 25 mg * Treatment C is dapagliflozin 10 mg

Study Record Dates

• First Submitted: June 15, 2021
• First Posted: July 9, 2021
• Study Start: June 17, 2021
• Primary Completion: February 2, 2022
• Study Completion: July 19, 2022
• Last Updated: July 28, 2022

Record last verified: 2022-07

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)