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Diabetes Mellitus, Type 2Phase 1NCT01013766

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

A Phase 1 study testing GSK1362885 in people with Diabetes Mellitus, Type 2, run by GlaxoSmithKline at 2 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 to 65 years
Conditions the study is for
Diabetes Mellitus, Type 2
What is being tested?
GSK1362885
Could I receive a placebo?
No, everyone receives an active treatment
How many people
23 participants
Where
2 sitesUnited States
Study dates
13 Aug 2009to 20 Nov 2009
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 65 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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:
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  • 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.

Who cannot join

  • 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.
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  • 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.
  • Gastrointestinal surgery surgery within the past 6 months for laparotomy or past 3 months for laparoscopy including cholecystectomy
  • Chronic or acute pancreatitis within the past year.
  • History of regular alcohol consumption averaging greater than 7 drinks/week for women or greater than 14 drinks/week for men. 1 drink is equivalent to (12 g alcohol) = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of 80 proof distilled spirits) within 6 months of screening.
  • Smoked or used tobacco or nicotine-containing products within the previous 6 months.
  • Has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of current study medication.
  • Exposure to more than four new chemical entities within 12 months prior to the first dosing day.
  • Is taking prohibited medications. See Section 9 for a detailed list of prohibited medications. Note also:
  • The use of anti-diabetic agents other than those listed in Inclusion #6 is reason for exclusion and subjects will not be allowed to wash off of unapproved anti-diabetic medications in order to qualify for participation in this study.
  • Subjects must wash out from the following medications during the 10-day period prior to first dose, and must remain off these medications through discharge on Day 7: all antidiabetic medications specified in Inclusion #6, all statin agents, fat absorption blocking agents, and bile acid sequestrants. Fibrates must be washed out for a 14-day period prior to first dose.
  • Vitamins, herbal and dietary supplements (including St John's Wort) are prohibited within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication and through discharge on Day 7.
  • Unwilling to abstain from
  • Caffeine-or xanthine-containing products for 24 hours prior to dosing until Day 7
  • Use of illicit drugs or nicotine-containing products
  • Alcohol for 24 hours prior to dosing until Day 7
  • Consumption of red wine, Seville oranges, grapefruit or grapefruit juice from 7 days prior to the first dose of study medication until collection of the final pharmacokinetic blood samples
  • History of sensitivity to any of the study medications, or components thereof or a history of drug or other allergy that, in the opinion of the physician responsible, contraindicates their participation. This includes sensitivity to heparin, if heparin will be used to maintain catheter patency.
  • Where participation in the study would result in donation of blood in excess of 500 mL within a 56 day period.
  • Subject is either an immediate family member of a participating investigator, study coordinator, employee of an investigator; or is a member of the staff conducting the study.
  • Unwillingness or inability to follow the procedures outlined in the protocol.
  • Individual or family history of glycogen storage disease.

Trial locations and contacts

2 sites in 1 country.

United States2 sites

  • GSK Investigational Site

    Phoenix, Arizona, 85013

  • GSK Investigational Site

    Saint Paul, Minnesota, 55114-1067

Other trials in United States

About this study

Official title: A Randomized, Open-Label Study to Evaluate the Safety,Tolerability, Pharmacokinetics, and Pharmacodynamics ofGSK1362885 in Subjects With Type 2 Diabetes Mellitus

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.

Read the detailed description

This is the first administration of single doses of GSK1362885 to the target population with T2DM. Based on the mechanism of action which involves reducing hepatic glucose output, it is possible that day time (AM) or night time (PM) dosing of GSK1362885 could produce different plasma glucose lowering effects, acting either on prandial or post-absorptive elevations of HGO. This study is designed to compare glucose profiles following AM and PM doses to determine if there is any advantage to either one. This study will compare glucose profiles following a single dose of GSK1362885 in the morning before breakfast (AM) to a single dose administered at night (PM). These two dosing periods will be randomized and each subject will receive both dosing regimens. A third dosing period (BID) is not randomized, but is included to explore the effects of GSK1362885 on glucose profiles when administered twice daily in a 24 hour timeframe.

Being tested
GSK1362885
Keywords
GSK1362885, Pharmacodynamics, Safety, Pharmacokinetics, T2DM, Tolerability
Medical subject headings
Diabetes Mellitus, Type 2

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • GSK1362885Drug

    100mg in the AM, 100mg in the PM, 50mg BID

  • GSK1362885Drug

    100mg in the PM, 100mg in the AM, 50mg BID

Study groups in NCT01013766
Study groupRoleWhat they receive
AM/PM/BIDOtherSubjects will receive a dose of 100mg in the AM on Day 1, followed by a dose of 100mg in the PM on Day 4, and a dose of 50mg BID on Day 6.
Receives: Drug: GSK1362885
PM/AM/BIDOtherSubjects will receive a dose of 100mg in the PM on Day 1, followed by a dose of 100mg in the AM on Day 4, followed by 50mg BID on Day 6.
Receives: Drug: GSK1362885

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Safety and tolerability assessments including adverse events and clinical laboratory tests

    Measured: 7 Days

  2. Pharmacodynamics following oral administration (glucose, insulin, c-peptide)

    Measured: 24 hours

  3. Pharmacokinetic parameters: AUC, Cmax, Tmax, t1/2, tlag, Cl/F, and V/F

    Measured: 24 hours

Secondary outcomes (2)

  1. Pharmacodynamics following BID administration (glucose, insulin, c-peptide)

    Measured: 24 hours

  2. Relationship between pharmacokinetic and pharmacodynamic parameters

    Measured: 24 hours

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Nov 2009 (estimated)
  2. Study start13 Aug 2009
  3. Primary completion20 Nov 2009
  4. Study completion20 Nov 2009

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
23 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01013766
Sponsor's protocol ID
111823
Status last verified
Jun 2017
First submitted
29 Oct 2009
Last updated
20 Jun 2017
Results posted
No
Data monitoring committee
No
Individual data sharing
Yes: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing GSK1362885 in people with Diabetes Mellitus, Type 2, run by GlaxoSmithKline at 2 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 45 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 20 Jun 2017. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Safety and tolerability assessments including adverse events and clinical laboratory tests (time frame: 7 Days). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01013766.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Jun 2017.

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