Bridging Study With GSK239512 In Patients With Mild To Moderate Alzheimer's Disease

• Register: ClinicalTrials.gov
• Last refreshed on: 17 October 2012
• Main ID: NCT00675090
• Date of registration: 24/04/2008
• Primary sponsor: GlaxoSmithKline
• Public title: Bridging Study With GSK239512 In Patients With Mild To Moderate Alzheimer's Disease
• Scientific title: A Single Blind, Placebo-controlled, Randomised Study in Mild to Moderate Alzheimer's Disease Patients to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of GSK239512, a Selective Histamine H3 Receptor Antagonist
• Date of first enrolment: February 2008
• Target sample size: 28
• Recruitment status: Completed
• URL: http://clinicaltrials.gov/show/NCT00675090
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Double Blind (Subject, Investigator), Primary Purpose: Treatment

Countries of recruitment

Australia, Czech Republic, Korea, Republic of, United Kingdom

Contacts

• Name: GSK Clinical Trials
• Affiliation: GlaxoSmithKline

Key inclusion & exclusion criteria

Inclusion Criteria:

- Male or female subjects with a clinical diagnosis of probable Alzheimer's disease

- The subject has an MMSE score at screening of 12 to 26 for Part A and 16-26 for Part
B.

- Age = 50 and above.

- If female, the subject must be post-menopausal (i.e. 12 months without menstrual
period) or surgically sterile.

- Male subjects must be willing to abstain from sexual intercourse with pregnant or
lactating women; or be willing to use a condom/spermicide in addition to having their
female partner use another form of contraception if the woman could become pregnant,
from the time of the first dose of GSK239512 until 84 days following completion of
the study.

- The subject has the ability to comply with the study procedures.

- The subject has a permanent caregiver and is willing to attend all study visits for
Parts A and B.

- The subject has provided full written informed consent prior to the performance of
any protocol specific procedure, or if unable to provide informed consent due to
cognitive status, full written informed consent on behalf of the subject has been
provided by a legally acceptable representative.

- The caregiver has provided his / her written consent prior to the performance of any
protocol specific procedure.

Exclusion Criteria:

- In the opinion of the investigator, following review of CT/MRI scans in the past 12
months and completion of neurological review there could be other probable causes of
dementia

- 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, or current depression (a score of =8 on the Cornell Scale for
Depression in Dementia), or subjects with other psychiatric features in their AD
which would in the opinion of the investigator, would increase risk to safety.

- History of significant sleep disturbance, for example, when it is associated with
nocturnal wandering, nocturnal confusion / disorientation / agitation, which in the
opinion of the investigator, may increase safety risk.

- History or presence of known or suspected seizures, unexplained significant loss of
consciousness within last 6 months. Subjects who had febrile seizures in childhood
may be included if these ceased by age 10 and they have had no other type of seizure
in their medical history and have not been on anti-epileptic medications.

- History or presence of significant cardiovascular, 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, medical or psychiatric condition, which, in the opinion of the
Investigator, makes the subject unsuitable for inclusion in the study.

- History of alcohol or other substance abuse, according to the Diagnostic and
Statistical Manual of Mental Disorders - Substance related disorders (DSM-IV)
criteria.

- Clinically significant abnormalities in laboratory tests, including subjects with
active liver disease or uncontrolled thyroid disease.

- Uncontrolled hypertension with systolic BP =160 and/or diastolic =95 mmHg. Subjects
with controlled hypertension with systolic BP < 160 mmHg and diastolic <95 mmHg for
at least 4 weeks are acceptable.

- Systolic BP <100 mmHg and/or diastolic <60 mmHg.

- Subjects with ECG criteria outside ranges specified in the protocol

- History of hypersensitivity to GSK239512 or its excipients.

- Treatment with cholinesterase inhibitors, (including Tacrine), memantine or
selegiline within the previous month. No patients with AD who are already on these
medications at the time of screening will be recruited, as it would be unethical to
withdraw these medications for study participation. Only AD subjects who are not yet
on these medications, or who have withdrawn from these medications for other reasons
previously, may be enrolled into this study.

- Subjects who are currently taking or who have taken in the last month anti-psychotic
drugs (typical or atypical dopaminergic antagonists or modulators) or mood
stabilization drugs (including SSRI, DNRI, SNRI, MAO inhibitors, tricyclic
antidepressants, lithium, valproate, carbamazepine).

- Subjects who are currently taking Pgp inhibitors or any CYP3A4 inhibitors.

- Subjects on chronic sedative medications (= 4 days per week for the past 4 weeks).

- Subject or caregiver is an immediate family member or employee of the participating
Investigator, any of the participating site staff or GSK staff.

- Has received any other investigational treatment in the previous 3 months.



Age minimum: 50 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Alzheimer's Disease

Mild to Moderate Alzheimers Disease

Intervention(s)

Drug: GSK239512

Drug: Placebo

Primary Outcome(s)

Safety and tolerability as measured by adverse events, vital signs clinical laboratory measurements and validated clinical assessment scales. [Time Frame: Days 8, 15, 22 and 29]

Secondary Outcome(s)

Pharmacodynamics measured by computerized cognitive tests and validated clinical rating scales. Also investigating the Pharmacokineticsat trough concentrations (Cmin) after GSK239512 repeat dosing on days 8, 15, 22 and 29 and 15. [Time Frame: days 8, 15, 22 and 29]

Secondary ID(s)

H3B109689

Source(s) of Monetary Support

Please refer to primary and secondary sponsors