Mild Alzheimer''s Disease to Assess the of Extended Release Formulation of Rosiglitazone (RSG XR)

NCT00688207 | Completed Phase 1

• 1 other identifier: AVA109941
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

Brief Summary

The present pharmacokinetic study is designed to assess the pharmacokinetics of RSG XR as monotherapy in patients with mild Alzheimer's disease (AD) as such information will not be obtained from the current phase III trials . The study aims to enroll fourteen patients (seven of each APOE genotype). Each patient will receive a single oral dose of 4mg of RSG XR in the morning under fasted conditions and PK samples will be taken up to 36h.

Conditions

Alzheimer's Disease

Keywords

PPAR agonist,; Rosiglitazone XR,; BRL-049653.; Alzheimer's disease,

Outcome Measures

Primary Outcomes (1)

• AUC (0-inf) and Cmax of RSG XR

  Up to 36 hours

Secondary Outcomes (1)

• AUC(0-t), t1/2 and tmax for RSG XR

  Up to 36 hours

Study Arms (1)

Rosiglitazone

EXPERIMENTAL

An open-label, single, oral dose of 4mg of rosiglitazone in the morning under fasted conditions

Drug: Rosiglitazone (Extended Release)

Interventions

Rosiglitazone (Extended Release) DRUG

open-label, single, oral, 4mg dose

Rosiglitazone

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female subjects with a clinical diagnosis of probable Alzheimer's disease in
• accordance with NINCDS-ADRDA3 criteria for at least 3 months
• Subject has mild Alzheimer's disease as defined by a MMSE score 18 to 26 inclusive
• at Screening
• Hachinski Ischemia Score ≤ 4 at Screening
• Subjects aged ≥50 and ≤90 years.
• Subject has not taken an approved Alzheimer's therapy in the last 30 days.
• Current use of medication is in accordance with the criteria listed in Section 9.1).
• Female subjects must be post-menopausal (i.e. \>1 year without menstrual period),
• surgically sterile, or agree to use adequate method of contraception for the duration of the study.
• Female subjects who are pre-menopausal or who have been postmenopausal for \<1 year must undertake pregnancy testing at screening, which must
• be negative. More than one pregnancy test may be required (i.e., when the time period between enrolment and study treatment is \> 7 days).
• Pregnancy testing will be performed at screening, pre-dose (Day 1) and follow-up visit for all women of child-bearing potential and those who have been postmenopausal for less than 1 year. If clinically indicated, a urine or serum pregnancy test may be performed at anytime during the study.
• Brain CT or MRI scan performed within the past 12 months or at Screening, showing no evidence of any other potential cause of dementia other than Alzheimer's disease.
• Neurological exam without focal changes (excluding changes attributable to AD or peripheral trauma).

You may not qualify if:

• Diagnosis of possible, probable, or definite vascular dementia in accordance with NINDS-AIREN6 criteria
• History or evidence of any other CNS disorder that could be interpreted as a cause of dementia: e.g. cerebrovascular disease (stroke, hemorrhage), structural abnormality, epilepsy, infectious or inflammatory/demyelinating CNS conditions, Parkinson's disease.
• Evidence of the following disorders: current vitamin B12 deficiency, positive syphilis serology or active thyroid dysfunction (particularly that suggestive of hypothyroidism), including abnormally high or low serum levels of thyroid stimulating hormone (TSH) that is clinically significant in the opinion of the investigator.
• History of Type 1 diabetes mellitus or secondary diabetes mellitus.
• Type 2 diabetes mellitus where the subject is being treated with insulin, a PPARγ agonist, or an insulin secretagogue (e.g. a sulfonylurea or glitinide).
• Any patient with an HbA1c ≥8.5%
• History or clinical/laboratory evidence congestive heart failure defined by the New York Heart Association criteria (Class I to IV cardiac status) (Appendix 4).
• History of cardiovascular event within the last 6 months (i.e. intervention, percutaneous coronary intervention, vascular surgery, acute coronary syndrome \[non Q-wave myocardial infarction, Q-wave myocardial infarction, unstable angina\] or significant arrhythmia; or major intervention (e.g. cardiac surgery or angiography plus stenting) scheduled).
• History of significant psychiatric illness such as schizophrenia or bipolar affective disorder that in the opinion of the Investigator would interfere with participation in the study, major depressive disorder (according to DSM-IV) in the past year, or current active depression requiring initiation of treatment.
• Clinically significant peripheral oedema at the time of screening.
• Current or recent drug or alcohol abuse or dependence (defined by DSM-IV criteria for substance-related disorders), or recent or remote history of the same if that could be a contributing factor to the dementia.
• Systolic blood pressure \>165 or \<90 mmHg or diastolic blood pressure \>95 or \<60 mmHg at the time of screening.
• Clinically significant anaemia (i.e. haemoglobin \<11 g/dL for males or \<10 g/dL for females)
• Patients with GFR ≤50ml/min (assessed by Cockcroft-Gault method ) .
• ALT, AST, or alkaline phosphatase values \>2.5 times the upper limit of normal, total bilirubin values \>1.5 times the upper limit of normal, or history of severe hepatobiliary disease (e.g. hepatitis B or C, or cirrhosis, Child-Pugh Class B/C).

Sponsors & Collaborators

• GlaxoSmithKline: lead

Study Sites (1)

GSK Investigational Site

Berlin, State of Berlin, 10117, Germany

Location

Related Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Rosiglitazone

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Thiazolidinediones; Thiazoles; Sulfur Compounds; Organic Chemicals; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• GSK Clinical Trials

  GlaxoSmithKline

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 28, 2008
• First Posted: June 2, 2008
• Study Start: April 1, 2008
• Primary Completion: September 1, 2008
• Study Completion: September 1, 2008
• Last Updated: November 7, 2016

Record last verified: 2016-11

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)