Study of BMF-219 in Healthy Adult Subjects and in Adult Subjects With Type 2 Diabetes Mellitus (T2D)

Korábbi kezelés

• Receiving an investigational intervention or having participated in another clinical trial within 30 days.
• Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
• Received prior menin inhibitor treatment.
  • Subjects with T2D (MAD Cohorts) Exclusion Criteria:
• Type 1 Diabetes Mellitus or a secondary form of diabetes or any prior history of diabetic ketoacidosis.
• Have had recurrence (≥2 episodes) of severe hypoglycemia (defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery) within the last 6 months prior to screening or, has a history of hypoglycemia unawareness or poor recognition of hypoglycemic symptoms as judged by the Investigator.
• Use of anti-diabetes medications (sulfonylureas, insulin, dipeptidyl peptidase-IV inhibitor [DPP-4I] [linagliptin and saxagliptin only] thiazolidinediones) within last 2 months prior to screening.
• Active HBV or active HCV at screening. Known positive test, if any, prior to screening or history of HIV. An active COVID-19 infection at screening.
• TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
• Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.
  • Subjects with T2D (Expansion Cohort) Exclusion Criteria:
• Prior history of diabetic ketoacidosis or hyperosmolar coma.
• History of severe hypoglycemia (defined by the occurrence of neuroglycopenic symptoms requiring the assistance of another person for recovery) within the last 6 months prior to screening or, has a history of hypoglycemia unawareness.
• Use of any of the following anti-diabetes medications within 2 months prior to screening: sulfonylureas, insulin, and the dipeptidyl peptidase-4 inhibitors (DPP4i) linagliptin and saxagliptin (sitagliptin and other DPP4i allowed) thiazolidinones [TZD]) within last 2 months prior to screening.
• TSH >6 mIU/L or <0.4 mIU/L (on stable thyroid replacement dose for 3 months prior to screening).
• Currently dieting (formal weight loss program) and/or are currently using or have used within 2 months of screening any drugs for weight management.

Más betegség

• Evidence or history of any clinically significant disease or malignancy.
• History of hypertension or untreated hypertension (sitting systolic blood pressure (BP) ≥140 and diastolic BP ≥90 mm Hg).
• History of stomach or intestinal surgery or resection (except appendectomy, hernia repair, and/or cholecystectomy).
• A history or evidence of HIV, HCV, or HBV infection at screening or active COVID-19 infection on screening.
• Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg).
• History of stomach or intestinal surgery or resection and/or gastroparesis (except that appendectomy, hernia repair, and/or cholecystectomy will be allowed).
• History of cirrhosis.
• Type 1 Diabetes Mellitus or a secondary form of diabetes.
• Active HBV or active HCV at screening. Known positive test or history of HIV. An active COVID-19 infection at screening.
• Severe uncontrolled treated or untreated hypertension (systolic blood pressure >150 mmHg or diastolic blood pressure >90 mmHg).
• History of stomach or intestinal surgery or resection and/or gastroparesis.
• History of cirrhosis.

Laborértékek

• Mean QTcF ≥ 440 msec on triplicate ECGs. Use of medications known to significantly prolong the QT or QTcF interval.
• Fasting plasma glucose ≥255 mg/dL, fasting C-peptide <0.8 ng/mL, fasting insulin >55 μIU/mL.
• Mean QTcF ≥450 ms. Use of medications known to significantly prolong the QT or QTc interval.
• Fasting triglyceride ≥500 mg/dL.
• Have an eGFR <60 mL/min/1.73 Equation at screening.
• AST or ALT > 1.5 × ULN, bilirubin > 1.5 × ULN. Isolated GGT elevation >2.5 ULN without > 1.5 x ULN AST, ALT and/or total bilirubin but with a history of abnormal LFTs in the last 6 months or a medical history of a liver disorder should be excluded.
• History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 x ULN.
• Fasting plasma glucose ≥255 mg/dL, fasting C-peptide <0.8 ng/mL, fasting insulin >55 μIU/mL.
• Mean QTcF interval >450 ms on triplicate ECGs. Use of prescription or over-the-counter medications known to significantly prolong the QT or QTc interval is excluded.
• Fasting triglyceride ≥500 mg/dL.
• eGFR<60 mL/min/1.73.
• AST or ALT >1.5 × ULN, Total bilirubin >1.5 × ULN at screening.
• History of acute or chronic pancreatitis and serum lipase and/or amylase above 1.5 x ULN.

Egyéb

• Healthy Subject Exclusion Criteria:
• Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
• Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1.
• Known self or family history (first-degree relative) of multiple endocrine neoplasia Type 1 (MEN1).

• Healthy Subject Inclusion Criteria:
• Males or females, age ≥18 and ≤65 years.
• BMI ≥18 and ≤35 kg/m2.
• Subjects are healthy on the basis of their medical history, physical examination, ECG, and routine laboratory data.
• All subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.
  • Subjects with T2D: (MAD Cohorts) Inclusion Criteria:
• Males or females, age ≥18 and ≤65 years.
• Diagnosed with T2D within the last 15 years.
• Treated with lifestyle management with or without at the most 3 anti-diabetic medications with a stable dose for at least 2 months prior to screening. If on metformin, the stable dose should be at least 500mg/day.
• HbA1c ≥7.0% and ≤10.5%.
• BMI ≥25 and ≤40 kg/m2.
• Females are to be not pregnant, non-lactating.
• All Subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.
  • Subjects with T2D: (Expansion Cohort) Inclusion Criteria:
• Males or females, age ≥18 and ≤65 years.
• Diagnosed with T2D within the last 7 years.
• Treated with lifestyle management with or without at the most 3 anti-diabetic medications with a stable dose for at least 2 months prior to screening. If on metformin, the stable dose should be at least 500mg/day.
• HbA1c ≥7.0% and ≤10.5%.
• BMI ≥25 and ≤40 kg/m2.
• Females are to be not pregnant, non-lactating.
• All Subjects must be willing and able to provide written, signed informed consent and be willing and able to comply with all study procedures and tests.