A Study to Evaluate the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of GSK1362885 in Type 2 Diabetics

Completed · Phase 1

Conditions studied: Diabetes Mellitus, Type 2

In brief

This study is the second administration of GSK1362885 in humans. GSK1362885 is a novel, potent inhibitor of human glycogen phosphorylase (GP) under development for the treatment of type 2 diabetes mellitus (T2DM). This study will investigate the compound's safety, tolerability, pharmacokinetics, and pharmacodynamics in subjects with Type 2 Diabetes Mellitus.

Key facts

Study ID

NCT01013766

Run by

GlaxoSmithKline

People needed

23

Starts

2009-08-13

Expected to finish

2009-11-20

Last updated by the study team

2017-06-20

Who can join

Age: 18 and older, up to 65. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• A subject will be eligible for inclusion in this study only if all of the following criteria apply:
• A diagnosis of T2DM as determined by a responsible physician based on a medical evaluation including medical history, physical examination, and laboratory tests. Subjects may be entered if they have stable hypertension or hyperlipidemia on therapy. Subjects with other conditions except as noted in Exclusion Criteria may be included only if the Investigator and the GSK medical Monitor agree that the condition is unlikely to introduce additional risk factors and will not interfere with the study procedures.
• Male or female between 18 and 65 years of age, inclusive, at the time of signing the informed consent.
• A female subject is eligible to participate if she is of non-childbearing potential, defined as pre-menopausal females with a documented tubal ligation or hysterectomy; or postmenopausal/premature ovarian failure defined as 12 months of spontaneous amenorrhea. FSH and estradiol levels will be checked at Screening for postmenopausal women. Simultaneous follicle stimulating hormone (FSH) greater than 40 MlU/ml and estradiol less than 40 pg/ml (<140 pmol/L) is confirmatory.
• BMI within the range 22 to 38 kg/m2 (inclusive).
• T2DM diagnosed at least 3 months prior to Screening with:
• Fasting plasma glucose (FPG) level less than or equal to 250mg/dL at the Screening visit,
• FPG level less than or equal to 270 mg/dL on Day -2
• For subjects taking no antidiabetic medications: HbA1c between 6.5 and 11 percent, inclusive, at Screening visit
• For subjects taking one or two antidiabetic medications: HbA1c between 5.8 and 10 percent, inclusive, at Screening visit
• Subjects must be treating their T2DM using one of the following regimens:
• Diet and exercise therapy
• Metformin as monotherapy
• Sulfonylurea as monotherapy
• Metformin and sulfonylurea in combination, if one or both component(s) is being administered at a dose that is less than the maximum dose
• DPP-IV inhibitors, either as monotherapy, or in combination with other agent(s) on this list, if one or both component(s) is being administered at a dose that is less than the maximum dose
• Exenatide, either as monotherapy or in combination with other agent(s) on this list, if one or both component(s) is being administered at a dose that is less than the maximum dose
• All doses of anti-diabetic medication must have been stable for at least 2 months prior to Screening, and the subject must be willing to wash out from their antidiabetic medications from Day -10 through Day 7.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.

You may not qualify if…

• A subject will not be eligible for inclusion in this study if any of the following criteria apply:
• Has any of the following laboratory abnormalities:
• Positive pre-study Hepatitis B surface antigen or positive Hepatitis C result within 3 months of screening.
• Positive test for HIV antibody
• History of uncorrected thyroid dysfunction or an abnormal thyroid function test assessed by TSH at Screening. (NOTE: subjects with hypothyroidism on a stable dose of thyroid replacement therapy for at least 3 months prior to Screening and who have a screening thyroid stimulating hormone (TSH) within the normal range may participate.)
• A positive pre-study drug/urine screen. A minimum list of drugs that will be screened for include amphetamines, barbiturates, cocaine, opiates, cannabinoids and benzodiazepines.
• A pre-study urine cotinine screen indicating use of tobacco/ nicotine containing products.
• Subjects with values outside the specified ranges for the following Key Clinical Laboratory Tests must be excluded from the study. Laboratory tests may be repeated once at the discretion of the investigator.
• Liver function tests: ALT, Direct Bilirubin, or Albumin more than 10 percent outside the normal reference range (less than 0.9 x LLN or greater than 1.1 x ULN)
• Electrolytes: Sodium more than 5mEq/L outside the normal reference range, Potassium or Calcium more than 10 percent outside the normal reference range (less than 0.9x LLN or greater than 1.1 x ULN)
• Fasting Total Cholesterol greater than 240mg/dL, or Triglycerides greater than 450mg/dL
• Muscle: CPK greater than 1.5 x ULN
• Hematology: Hemoglobin, WBC, Neutrophils, or Platelets more than 10 percent outside the normal reference range (less than 0.9 x LLN or greater than 1.1 x ULN)
• Significant renal disease as manifested by one or more of the following:
• Creatinine clearance less than 60 mL/min.
• Urine protein/creatinine (mg/mg) ratio greater than 2.5; or urine albumin concentration greater than 300 ug/mg of creatinine.
• Known loss of a kidney either by surgical ablation, injury, or disease
• Other Clinical Laboratory Tests, not listed as a Key Clinical Laboratory Tests in Exclusion Criterion #4, should also be considered by the Investigator in the overall evaluation of a subject's suitability for enrollment in the study.
• Significant ECG abnormalities as defined per protocol
• Resting systolic blood pressure less than 80 mmHg or greater than 150 mmHg or diastolic blood pressure less than 60 mmHg or greater than 95 mmHg at screening. Blood pressure assessments may be repeated once if needed, allowing adequate time for subject to rest.
• Previous use of insulin as a treatment within 3 months of Screening, or for greater than 2 weeks when used for acute illness in the last 12 months prior to Screening, or if used for more than 1 year when associated with GDM.
• Has a history of any of the following conditions:
• Clinically significant symptoms of gastroparesis.
• Cholelithiasis or obstructive or inflammatory gallbladder disease within 3 months prior to Screening.
• Gastrointestinal disease that could affect fat or bile acid absorption, including inflammatory bowel disease, chronic diarrhea, Crohn's or malabsorption syndromes within the past year.

Where it is running

• GSK Investigational Site — Phoenix, Arizona, United States
• GSK Investigational Site — Saint Paul, Minnesota, United States

Full record on ClinicalTrials.gov

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