TAK-329 Glucose Clamp Study

NCT01311076 | Completed Phase 1

• 2 other identifiers: TAK-329_102U1111-1119-7141
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Type 1 Diabetes Mellitus

Keywords

Type 1 Diabetes Mellitus; Insulin; Glucose; Drug Therapy

Outcome Measures

Primary Outcomes (3)

• (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.

  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.

  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.

  On Day 1 in Four Treatment Periods.

Secondary Outcomes (4)

• Maximum Observed Pharmacodynamic Response (Emax) of Cortisol During Hypoglycemic Clamp.

  On Day 1 in Four Treatment Periods.

• Area under the effect versus time curves (AUEC) of Cortisol During Hypoglycemic Clamp.

  On Day 1 in Four Treatment Periods.

• Incidence of Treatment-Emergent Adverse Events.

  After receiving first dose of study drug and within 30 days after receiving the last dose of study drug.

• Incidence of Hypoglycemia.

  After receiving first dose of study drug and Day 7 +/-2 after receiving the last dose of study drug.

Study Arms (4)

TAK-329 50 mg

EXPERIMENTAL

Drug: TAK-329

TAK-329 200 mg

EXPERIMENTAL

Drug: TAK-329

Insulin 0.2 U/kg

ACTIVE COMPARATOR

Drug: Insulin

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

TAK-329 DRUG

TAK-329 50 mg, tablets, orally, single dose, one day.

TAK-329 50 mg

Insulin DRUG

Insulin 0.2 U/kg, subcutaneous injection, single dose, one day.

Also known as: Insulin lispro, Humalog

Insulin 0.2 U/kg

Placebo DRUG

TAK-329 placebo-matching tablets, orally, single dose, one day.

Placebo

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• In the opinion of the investigator, the participant or legal guardian is capable of understanding and complying with protocol requirements.
• The participant or, when applicable, the participant's legally acceptable representative signs and dates a written, informed consent form and any required privacy authorization prior to the initiation of any study procedures.
• Is an adult female or an adult male with Type 1 Diabetes Mellitus (diagnosed at least 1 year prior to Screening) with a glycosylated hemoglobin ≤10.0%.
• Is aged 18 to 50 years, inclusive, at the time of informed consent and first dose of study drug.
• Weighs at least 50 kg and has a body mass index between 18.0 and 32.0 kg/m2, inclusive at Screening.
• Males who are nonsterilized and sexually active with a female partner of childbearing potential agree to use adequate contraception from signing of informed consent throughout the duration of the study and for 12 weeks after the last dose.
• A female participant, including women of childbearing potential, who is sexually active with a nonsterilized male partner agree to use consistently use contraception from signing of informed consent throughout the duration of the study.
• Was treated with insulin either in the form of multiple daily injections or as continuous subcutaneous insulin infusion (CSII or "insulin pump") for at least 3 months prior to Screening.
• Has a fasting serum C-peptide ≤0.2 nmol/L at Screening.
• The participant, if taking concomitant medications for stable disease, has been on a stable dose for a minimum of 60 days prior to Day 1 of Period 1 and the medications are approved by the investigator and the Takeda Medical Monitor.
• A female participant of child-bearing potential, if using hormonal contraception, has been on stable hormonal contraception (without changes to the dose or type of preparation) for at least 6 months prior to Screening.

You may not qualify if:

• The participant is participating in another investigational study or has taken any investigational drug within 30 days prior to Day -1.
• Has donated blood or experienced acute blood loss (including plasmapheresis) of more than 500 mL within 56 days prior to Day -1.
• Has a history or clinical manifestations of clinically significant metabolic (including Type 2 Diabetes Mellitus, hypercholesterolemia or dyslipidemia but excluding Type 1 Diabetes Mellitus), endocrinologic, hematologic, pulmonary, cardiovascular, gastrointestinal, neurologic, hepatic, renal, urologic, immunologic, glaucoma, or psychiatric disorders, or tendency for urinary retention.
• Has a known hypersensitivity to TAK-329, any of its excipients, any compound related to TAK-329, or known hypersensitivity to sulfonamides.
• Has a history of cataract (including traumatic) or glaucoma or has a positive ophthalmic examination with findings suggestive of a cataract within 7 days prior to or at Check in (Day -1) of Period 1.
• Has a history indicative of proliferative retinopathy or maculopathy and/or severe neuropathy including gastroparesis.
• Has a history of severe hypoglycemia requiring emergency medical attention less than 6 months prior to Screening or a medical history suggestive of hypoglycemia unawareness less than 1 year prior to Screening.
• Has a systolic blood pressure ≥145 mm Hg or a diastolic blood pressure ≥90 mm Hg that is confirmed by a repeat measurement taken at least 30 minutes apart at Screening and Check-in (Day -1) of Period 1.
• Has a history of drug abuse (defined as illicit drug use) or a history of alcohol abuse (defined as regular or daily consumption of more than 4 alcoholic drinks per day) within 2 years prior to Screening.
• Has an alanine transaminase or aspartate transaminase level of greater than 1.5 x the upper limit of normal at Screening or Check-in (Day -1), active liver disease, active gall bladder disease, or jaundice
• Has a thyroid stimulating hormone result out of the euthyroid range at Screening.
• Is on any non-insulin antidiabetic medication (including oral agents such as metformin or pioglitazone or injectables such as pramlintide or exenatide) or inhaled insulin within 90 days prior to Day -1 of Period 1.
• Has ingested foods or beverages containing grapefruit juice or Seville-type oranges within 14 days prior to Day 1 of Period 1 or any alcohol-or caffeine containing products or medications within 72 hours prior to Day 1 of each treatment period or anticipates an inability to abstain from these substances for the duration of the study.
• Has used any drug within 28 days prior to Day 1 of Period 1 that may interfere with the interpretation of study results or are known to cause clinically relevant interference with insulin action or glucose utilization.
• Has a history of cancer that has not been in remission for at least 5 years prior to the first dose of study drug. (This criterion does not include those subjects with basal cell or stage I squamous cell carcinoma of the skin.)

Sponsors & Collaborators

• Takeda: lead

Study Sites (1)

Unknown Facility

Chula Vista, California, United States

Location

MeSH Terms

Conditions

Diabetes Mellitus, Type 1; Insulin Resistance

Interventions

Insulin; Insulin Lispro

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Proinsulin; Insulins; Pancreatic Hormones; Peptide Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Peptides; Amino Acids, Peptides, and Proteins; Insulin, Short-Acting

Study Officials

• Associate Medical Director, Clinical Science

  Takeda

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 7, 2011
• First Posted: March 9, 2011
• Study Start: March 1, 2011
• Primary Completion: December 1, 2011
• Study Completion: January 1, 2012
• Last Updated: February 13, 2012

Record last verified: 2012-02

Locations

US (1)