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

An Open Label Single Oral Dose Study in Patients With Mild Alzheimer's Disease to Assess the Pharmacokinetics of Extended Release Formulation of Rosiglitazone (RSG XR) in This Population

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.

Study Overview

• Status: Completed
• Conditions: Alzheimer's Disease
• Intervention / Treatment: Drug: Rosiglitazone (Extended Release)

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Phase 1

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 10117
    • GSK Investigational Site

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 50 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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).
• Subjects who live with or who have a regular caregiver who is willing to attend all visits, oversee the subject's compliance with the protocol specified procedures and study medication, and who is willing to report on subject's status.
• Subject has provided full written informed consent prior to the performance of any protocol-specified procedure.
• Subjects considered for enrolment must have a QTc (either QTc B (Bazett's
• correction) or QTc F (Fridericia's correction)) <450msec at the Screening Visit, with the exception of subjects with bundle branch block (for whom either QTc B or QTc F must be <480msec).

Exclusion Criteria:

• 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.
• History or presence of gastro-intestinal, hepatic, or renal disease or other condition known to interfere with the absorption, distribution, metabolism, or excretion of drugs, or any other clinically relevant abnormality, which, in the opinion of the Investigator, makes the subject unsuitable for inclusion in the study.
• 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).
• History of a bone marrow transplant.
• Positive hepatitis B virus, hepatitis C virus or HIV test at screening.
• Subject is unable (with assistance, if appropriate) to take study medication or is at risk of non-compliance with study procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Rosiglitazone; An open-label, single, oral dose of 4mg of rosiglitazone in the morning under fasted conditions	Drug: Rosiglitazone (Extended Release); open-label, single, oral, 4mg dose

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
AUC (0-inf) and Cmax of RSG XR	Up to 36 hours

Secondary Outcome Measures

Outcome Measure	Time Frame
AUC(0-t), t1/2 and tmax for RSG XR	Up to 36 hours

Collaborators and Investigators

• Sponsor: GlaxoSmithKline

Publications and helpful links

Helpful 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.

Study record dates

Study Major Dates

• Study Start: April 1, 2008
• Primary Completion (Actual): September 1, 2008
• Study Completion (Actual): September 1, 2008

Study Registration Dates

• First Submitted: May 28, 2008
• First Submitted That Met QC Criteria: May 30, 2008
• First Posted (Estimate): June 2, 2008

Study Record Updates

• Last Update Posted (Estimate): November 6, 2016
• Last Update Submitted That Met QC Criteria: November 4, 2016
• Last Verified: November 1, 2016

More Information

Terms related to this study

• Keywords: Alzheimer's disease,; PPAR agonist,; Rosiglitazone XR,; BRL-049653.
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease; Hypoglycemic Agents; Physiological Effects of Drugs; Rosiglitazone
• Other Study ID Numbers: AVA109941

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Dataset Specification
   Information identifier: AVA109941
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Informed Consent Form
   Information identifier: AVA109941
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Study Protocol
   Information identifier: AVA109941
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Annotated Case Report Form
   Information identifier: AVA109941
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Individual Participant Data Set
   Information identifier: AVA109941
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Clinical Study Report
   Information identifier: AVA109941
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Statistical Analysis Plan
   Information identifier: AVA109941
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register