Effects of Triglycerides on Age-Related Cognitive Function Decline in Older Subjects

NCT ID: NCT01702480

Last Updated: 2017-05-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 116 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-11-05
• Study Completion Date: 2015-07-03

Brief Summary

This is a single centre, 2 part study in older subjects. Part 1 (Pharmacokinetic [PK] Assessment) is a double blind, randomized, placebo-controlled 4-period crossover study investigating the PK profile of four different doses of GSK2981710. Eight subjects will receive a single dose of GSK2981710 10 gram (g), 20 g, 30 g, 40 g or placebo in the morning and have PK assessments (every 0.5 hrs up to 8 hrs post-dose) throughout the day in each period. Each subject will complete a total of four dosing sessions and 4 days of PK assessments in 2 weeks. The Part 1 PK data will be used for dose selection and pharmacodynamic (PD) assessment period in Part 2. If the data from Part 1 is inconclusive, an additional 8 subjects may be recruited and Part 1 repeated (possibly dropping some doses) to increase confidence. A subject's total participation in Part 1 of the study will last a maximum of approximately 7 weeks including screening. Subjects who have completed Part 1 may be screened for eligibility and enrolled for Part 2.

Part 2 (PD Assessment) is a double blind randomized, placebo-controlled 2-period crossover design with 14-day treatment periods investigating the efficacy (cognitive performance) and tolerability (gastrointestinal [GI] side effects) of single daily dose of GSK2981710 selected from Part 1. Part 2 of the study will include the Screening period, two Baseline assessments (6-8 days before each Treatment period) and two 14-day treatment periods separated by a minimum 7-day washout period and follow-up visit of 3 to 5 days. Approximately 50 to 80 subjects will be randomized to either GSK2981710 or placebo. The PD assessments will be performed on 6 occasions for each subject: at 2 baselines (6 to 8 days before Day 1 of each treatment period), post-dose on the Day 1 of each treatment period to assess acute effects and on Day 15 of each treatment period (which is the day after the final dose) to assess chronic effects. A subject's total participation in Part 2 of the study will last approximately up to 12 weeks including screening.

Conditions

Alzheimer's Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Part 1: GSK2981710 10 gram (g)

Eight subjects will receive single dose of GSK2981710 in the form of 10 g medium-chain triglycerides (MCT) powder daily for 14 days.

Group Type: EXPERIMENTAL

GSK2981710

Intervention Type: DRUG

Will be available as 10 g medium-chain triglycerides (MCT) powder sachet that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Part 1: GSK2981710 20 g

Eight subjects will receive single dose of GSK2981710 in the form of 20 g MCT powder daily for 14 days.

Group Type: EXPERIMENTAL

GSK2981710

Intervention Type: DRUG

Will be available as 10 g medium-chain triglycerides (MCT) powder sachet that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Part 1: GSK2981710 30 g

Eight subjects will receive single dose of GSK2981710 in the form of 30 g MCT powder daily for 14 days.

Group Type: EXPERIMENTAL

GSK2981710

Intervention Type: DRUG

Will be available as 10 g medium-chain triglycerides (MCT) powder sachet that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Part 1: GSK2981710 40 g

Eight subjects will receive single dose of GSK2981710 in the form of 40 g MCT powder daily for 14 days.

Group Type: EXPERIMENTAL

GSK2981710

Intervention Type: DRUG

Will be available as 10 g medium-chain triglycerides (MCT) powder sachet that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Part 1: Placebo

Eight subjects will receive single dose of matching placebo daily for 14 days.

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Will be available as matching powder that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Part 2: GSK2981710 (dose to be decided from Part 1)

The subjects will receive single dose of GSK2981710 in the form of MCT powder (dose to be decided from Part 1) daily for 14 days.

Group Type: EXPERIMENTAL

GSK2981710

Intervention Type: DRUG

Will be available as 10 g medium-chain triglycerides (MCT) powder sachet that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Part 2: Placebo

The subjects will receive single dose of matching placebo daily for 14 days..

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Will be available as matching powder that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Interventions

GSK2981710

Will be available as 10 g medium-chain triglycerides (MCT) powder sachet that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Intervention Type: DRUG

Placebo

Will be available as matching powder that will be mixed with 125 - 250 milliliters (ml) water in a shaker and taken within 15 minutes of completion of breakfast

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

• Male or female individuals between the ages of 55 years and 80 years inclusive.
• 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 defined as 12 months of spontaneous amenorrhea. Child-bearing potential and has a negative pregnancy test on each of the testing visits.
• Body weight >=50 kilogram (kg) in males and >=40 kg in females. Body mass index (BMI) in the range 18.0 to 29.9 kg/meter (m)^2.
• Capable of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
• Sufficiently fluent in English that they are able to understand written and spoken instructions in the opinion of the investigator.
• Supine blood pressure between 110/70 to 150/90 millimetres of mercury (mmHg) inclusive at screening. Patients with a current history of hypertension who are controlled on a stable regimen for at least 3 months prior to the study and are asymptomatic can be included.
• 12 lead electrocardiogram (ECG) without any clinically significant abnormality as judged by the Investigator, and QT interval corrected using Bazett's formula (QTcB) or QT interval corrected using Fridericia's formula (QTcF) <=450 millisecond (msec)
• Suitable for cannulation and with adequate venous access
• Aspartate aminotransferase (AST), Alanine transaminase (ALT), alkaline phosphatase and bilirubin <= 1.5xULN (isolated bilirubin >1.5xULN is acceptable if bilirubin is fractionated and direct bilirubin <35%).
• For Part 2: Performs below the cut-off level on the Wechsler logical memory test below the mean level of performance of young, healthy adults.
• For Part 2: Otherwise normal neuropsychological performance as indicated by performance above the required level on the MINI Mental State Examination (MMSE) (a score of 27 or above is eligible).

Exclusion Criteria

• Previous or current medical condition, which as judged by the Investigator with consultation with the GSK Medical Monitor if required, may compromise subject safety or may interfere with the study procedures or the interpretation of data..
• Learning disability or learning disorder.
• Current history of Axis I psychiatric disorder as determined by MINI interview
• A drug dependence by the Diagnostic and Statistical Manual of Mental Disorders, Fourth (DSM-IV) criteria within the last 6 months as assessed by the Mini-international neuropsychiatric interview (MINI).
• A fall of at least 20 mm Hg systolic blood pressure within three minutes of standing upright at screening
• A positive pre-study human immunodeficiency virus (HIV), Hepatitis B surface antigen or positive Hepatitis C antibody result within 3 months of screening.
• Use of prescription or non-prescription drugs, including vitamins, herbal and dietary supplements (including St John's Wort) within 7 days or 5 half-lives (whichever is longer) prior to the first dose of study medication, unless in the opinion of the Investigator and GlaxoSmithKline (GSK) Medical Monitor the medication will not interfere with the study procedures or compromise subject safety.
• History of alcohol or substance abuse or dependence in the 6 months prior to screening as determined by the investigator. Abuse of alcohol, defined for males, as an average weekly intake of greater than 21 units (or an average daily intake of greater than 3 units), or defined for females, as an average weekly intake of greater than 14 units (or an average daily intake of greater than 2 units). One unit is equivalent to a half-pint (220 milliliters [mL]) of beer or 1 (25 mL) measure of spirits or 1 glass (125 mL) of wine.
• Current smokers defined as regular use of tobacco- or nicotine-containing products within 6 months prior to screening.
• Positive urine drug or alcohol breath test at screening or when tested at any of the study visits.
• Lactating females or pregnant females as determined by a positive urine/serum human chorionic gonadotropin (hCG) test at screening or when tested at any of the study visits.
• Where participation in the study would result in donation of blood or blood products in excess of 500 mL within a 90 day period.
• The subject has participated in a clinical trial and has received an investigational product within the following time period prior to the testing day in the current study: 90 days, 5 half-lives or twice the duration of the biological effect of the investigational product (whichever is longer).
• Lactose intolerant or allergic to milk or soy products
• The subject is on a diet including any diet that restricts or modifies intake of a particular type of food, e.g. carbohydrates, proteins, fats, or is on a ketogenic diet.
• Fasting Triglycerides equal to or more than 4.5 millimoles per litre; (mmol/L) at screening
• Subject who, in the investigator/designee's judgement, poses a significant suicide risk. Evidence of serious suicide risk may include any history of suicidal behaviour and/or any evidence of suicidal ideation on any questionnaires e.g. type 4 or 5 on the Columbia Suicide Severity Rating Scale (C-SSRS) in the last 6 months.
• History of sensitivity or allergy to drug or components thereof, or other allergy, that, in the opinion of the investigator or GSK Medical Monitor, contraindicates their participation.

• Minimum Eligible Age: 55 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

GlaxoSmithKline

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

GSK Clinical Trials

Role: STUDY_DIRECTOR

GlaxoSmithKline

Locations

GSK Investigational Site

Cambridge, Cambridgeshire, United Kingdom

Countries

United Kingdom

Other Identifiers

116713

Identifier Type: -

Identifier Source: org_study_id