Now Available: Final Rule for FDAAA 801 and NIH Policy on Clinical Trial Reporting

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

This study has been completed.
Information provided by (Responsible Party):
GlaxoSmithKline Identifier:
First received: April 24, 2008
Last updated: October 11, 2016
Last verified: October 2016
This is a safety and tolerability study to investigate the effect of GSK239512 on mild to moderate Alzheimers disease patients. The dose of GSK239512 will be titrated to reach the most well tolerated dose in the patients.

Condition Intervention Phase
Alzheimer's Disease
Drug: GSK239512
Drug: Placebo
Phase 1

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
Official 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

Resource links provided by NLM:

Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • 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 Measures:
  • 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 ]

Enrollment: 28
Study Start Date: February 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: GSK239512
GSK239512 oral tablets
Drug: GSK239512
GSK239512 oral tablets once a day
Placebo Comparator: Placebo
Placebo to match tablets
Drug: Placebo
Placebo tablets to match once a day


Ages Eligible for Study:   50 Years and older   (Adult, Senior)
Genders Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its identifier: NCT00675090

Australia, New South Wales
GSK Investigational Site
Randwick, New South Wales, Australia, 2031
Australia, Victoria
GSK Investigational Site
Heidelberg Heights, Victoria, Australia, 3084
Czech Republic
GSK Investigational Site
Prague 10, Czech Republic, 10100
Korea, Republic of
GSK Investigational Site
Seoul, Korea, Republic of, 110-744
GSK Investigational Site
Seoul, Korea, Republic of, 138-736
United Kingdom
GSK Investigational Site
Cambridgeshire, United Kingdom, CB2 2QQ
GSK Investigational Site
London, United Kingdom, SE1 1YR
GSK Investigational Site
Southall, United Kingdom, UB1 3HW
Sponsors and Collaborators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Additional Information:
Study Data/Documents: Dataset Specification  This link exits the site
Identifier: H3B109689
For additional information about this study please refer to the GSK Clinical Study Register
Individual Participant Data Set  This link exits the site
Identifier: H3B109689
For additional information about this study please refer to the GSK Clinical Study Register
Annotated Case Report Form  This link exits the site
Identifier: H3B109689
For additional information about this study please refer to the GSK Clinical Study Register
Informed Consent Form  This link exits the site
Identifier: H3B109689
For additional information about this study please refer to the GSK Clinical Study Register
Clinical Study Report  This link exits the site
Identifier: H3B109689
For additional information about this study please refer to the GSK Clinical Study Register
Study Protocol  This link exits the site
Identifier: H3B109689
For additional information about this study please refer to the GSK Clinical Study Register
Statistical Analysis Plan  This link exits the site
Identifier: H3B109689
For additional information about this study please refer to the GSK Clinical Study Register

Responsible Party: GlaxoSmithKline Identifier: NCT00675090     History of Changes
Other Study ID Numbers: H3B109689 
Study First Received: April 24, 2008
Last Updated: October 11, 2016
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
South Korea: Korea Food and Drug Administration (KFDA)
Australia: Department of Health and Ageing Therapeutic Goods Administration
Czech Republic: State Institute for Drug Control
Individual Participant Data  
Plan to Share IPD: Yes
Plan Description: Patient-level data for this study will be made available through following the timelines and process described on this site.

Keywords provided by GlaxoSmithKline:
Alzheimers Disease

Additional relevant MeSH terms:
Alzheimer Disease
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Neurodegenerative Diseases
Neurocognitive Disorders
Mental Disorders
Histamine H3 Antagonists
Histamine Antagonists
Histamine Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs processed this record on January 14, 2017