The purpose of this study is to compare the safety, tolerability, pharmacokinetic and pharmacodynamic properties of single doses of TAK-329 with a single dose of a subcutaneously-injected rapid-acting insulin analog in participants with type 1 diabetes mellitus.
Type 1 diabetes mellitus (T1DM), also known as insulin-dependent diabetes mellitus or juvenile-onset diabetes, occurs primarily due to β-cell destruction, usually leading to absolute insulin deficiency. The condition is immune-mediated and is usually idiopathic. Tight glycemic control using intensive insulin therapy was shown in the Diabetes Control and Complications Trial (DCCT) to reduce rates of microvascular complications in T1DM; however, achieving and maintaining such control in T1DM using standard insulin therapy requires a high level of support and is associated with increased potential for hypoglycemia, increased weight gain and, in some patients, aggravation of cardiovascular risk factors including dyslipidemia. TAK-329 is being developed by Takeda Global Research \& Development Center, Inc. (TGRD) as an adjunct treatment to improve glycemic control in patients with type 1 diabetes mellitus who use insulin therapy. This study will take place at 1 site in the United States. A total of 36 male and female adult participants with T1DM will take part in the study. The study will last about 77 days, including a 28 days screening period, 4 cross-over treatment periods and a follow up period. Participants will be confined to the study clinic for 2 days in each period. Participants will also be contacted by phone 30 days following the last dose of study drug.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Masking
QUADRUPLE
Enrollment
37
Unnamed facility
Chula Vista, California, United States
(AUCGIR 0-360): Area Under the Curve of the Glucose Infusion Rate From Time 0 to 360 minutes post dose Pharmacodynamic Parameter.
(AUCGIR 0-360) is measure of area under the curve of the glucose infusion rate from time 0 to 360 minutes (6 hours) post dose, measured in minutes during the glucose clamp procedure.
Time frame: On Day 1 in Four Treatment Periods.
GIRmax: Maximum Observed Glucose Infusion Rate Pharmacodynamic Parameter.
Maximum observed glucose infusion rate (GIRmax) is the peak glucose infusion rate of a drug after administration, obtained directly from the glucose infusion-time curve, measured in minutes during the glucose clamp procedure.
Time frame: On Day 1 in Four Treatment Periods.
TGIRmax: Time to Reach the Maximum Glucose Infusion Rate (GIRmax) Pharmacodynamic Parameter.
TGIRmax: Time to reach the maximum Glucose Infusion Rate (GIRmax), equal to time (hours) to GIRmax, measured in minutes during the glucose clamp procedure.
Time frame: On Day 1 in Four Treatment Periods.
Maximum Observed Pharmacodynamic Response (Emax) of Cortisol During Hypoglycemic Clamp.
The maximum observed increase or decrease (peak) effect for cortisol, based off sample collected at the start of the clamp procedure, 0 hours predose, and 0. 5, 1.0, 2, 3, 4 and 6 hours postdose. Hypoglycemic clamp procedure is a method for quantifying insulin secretion and resistance, used to measure glucose metabolism and insulin sensitivity.
Time frame: On Day 1 in Four Treatment Periods.
Area under the effect versus time curves (AUEC) of Cortisol During Hypoglycemic Clamp.
Area under the effect-time curve calculated using the linear trapezoidal rule for cortisol, based off sample collected at the start of the clamp procedure, 0 hours predose, and 0. 5, 1.0, 2, 3, 4 and 6 hours postdose. Hypoglycemic clamp procedure is a method for quantifying insulin secretion and resistance, used to measure glucose metabolism and insulin sensitivity.
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TAK-329 placebo-matching tablets, orally, single dose, one day.
Time frame: On Day 1 in Four Treatment Periods.
Incidence of Treatment-Emergent Adverse Events.
Incidence of treatment-emergent adverse events (TEAE) are adverse events with an onset that occurs after receiving study drug and within 30 days after receiving the last dose of study drug. A TEAE may also be a pretreatment adverse event or a concurrent medical condition diagnosed prior to the date of first dose of study drug that increases in severity after the start of dosing.
Time frame: After receiving first dose of study drug and within 30 days after receiving the last dose of study drug.
Incidence of Hypoglycemia.
Incidence of hypoglycemia (abnormal low blood sugar) classified into 4 categories: Severe Hypoglycemia (participant experiences confusion or disorientation requiring resuscitative action); Symptomatic Hypoglycemia (blood glucose of \<55 mg/dL accompanied by clinically significant signs and symptoms of hypoglycemia); Biochemical Hypoglycemia (blood glucose \<50 mg/dL preferably confirmed by second reading, regardless of accompanying symptoms or signs of hypoglycemia); and Other Hypoglycemia (any signs or symptoms considered by investigator indicative of hypoglycemia, regardless of glucose value).
Time frame: After receiving first dose of study drug and Day 7 +/-2 after receiving the last dose of study drug.