A Cardiac Safety Study of Galantamine in the Treatment of Alzheimer's Disease.

This study has been completed.
Sponsor:
Information provided by:
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
ClinicalTrials.gov Identifier:
NCT00309725
First received: March 31, 2006
Last updated: May 17, 2011
Last verified: January 2011
  Purpose

The objective of this trial was to investigate the effect of galantamine (an acetylcholinesterase inhibitor) on heart rate and PR interval (the time it takes for the heart's electrical impulse to get from the atria to the ventricles) during the administration of rapidly increasing doses and at the end of a 2-week treatment period with 32 mg per day in patients with Alzheimer's disease.


Condition Intervention Phase
Alzheimer's Disease
Drug: galantamine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Treatment
Official Title: Placebo-Controlled Evaluation of Galantamine in the Treatment of Alzheimer's Disease: A Cardiac Safety Study.

Resource links provided by NLM:


Further study details as provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:

Primary Outcome Measures:
  • Hourly mean heart rates and PR intervals during each of the 24-hour Holter monitoring periods; Twenty-four hour mean, minimum and maximum heart rates and PR intervals during each of the 24-hour Holter monitoring periods

Secondary Outcome Measures:
  • Pharmacokinetics and other safety parameters including ECG parameters were other parameters of interest.

Enrollment: 139
Study Completion Date: October 1999
Detailed Description:

This 6-week, double-blind, parallel group trial was also designed to detect cardiac arrhythmias and conduction disturbances, such as heart block. Holter monitors and Electrocardiograms were used to measure cardiac parameters at baseline, at the end of Week 2 (first dose of 12 mg twice daily), at the end of Week 4 (first dose of 16 mg twice daily) and at Week 6 (after 2 weeks of maximum tolerated dose allowed in the trial, i.e., 24 or 32 mg/day). Other safety data collected were adverse event reports, urine and blood analysis, vital signs and physical examination. Drug levels in the blood were also tested. Patients were randomized to receive either placebo or galantamine up to 32 mg daily (i.e., 4 mg twice daily in Week 1, 8 mg twice daily in Week 2, 12 mg twice daily in Weeks 3 and 4, and 16 mg twice daily in Weeks 5 and 6). Dosage could be reduced from 16 mg twice daily to 12 mg twice daily during the first 3 days of the 32 mg/day dosing period, if a patient could not tolerate the higher dose. This titration is more rapid and the dose is higher than currently recommended for treatment.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Outpatients diagnosed with Alzheimer's disease in accordance with NINCDS-ADRDA (National Institute of Neurological and Communicative Diseases and Stroke/Alzheimer's Disease and Related Disorders Association) classification for probable Alzheimer's disease
  • Mild/moderate dementia as evidenced by a Mini-Mental State Examination (MMSE) score ranging from 11 to 24, inclusive, at baseline
  • History of cognitive decline that has been gradual in onset and progressive over a period of at least 6 months
  • Evidence of sustained memory deterioration in an otherwise alert patient, plus additional impairment in at least one of these five areas: orientation, judgment and problem-solving, functioning in community affairs, functioning in home and hobbies, and functioning in personal care
  • Patients who live with or have regular daily visits from one or more responsible caregiver who are capable of assisting with the patient's medication, able to accompany the patient for assessments, and willing to provide information about the patient.On days that the patient was sent home with a Holter monitor, the caregiver was required to stay with the patient in the same household for the 24 hour duration of the cardiac assessment to ensure that the monitor lead placement remained intact. The caregiver was to be available the following day for the return of the Holter monitoring device
  • Patient or patient's relative, guardian or legal representative have signed the informed consent.

Exclusion Criteria:

  • Disorders such as Parkinson's disease, Pick's disease, or Huntington's chorea, Down's syndrome, Creutzfeldt-Jakob disease, Cushing's syndrome, or uncontrolled diabetes
  • Cognitive impairment resulting from trauma, injury, or hypoxia
  • Infection
  • Mental retardation or dementia or clinically active cerebrovascular disease
  • Current, clinically significant cardiovascular disease that would limit the patient's ability to complete a six-week trial.
  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 ClinicalTrials.gov identifier: NCT00309725

Sponsors and Collaborators
Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
Investigators
Study Director: Johnson & Johnson Pharmaceutical Research & Development, L.L. C. Clinical Trial Johnson & Johnson Pharmaceutical Research & Development, L.L.C.
  More Information

Additional Information:
No publications provided

ClinicalTrials.gov Identifier: NCT00309725     History of Changes
Other Study ID Numbers: CR012118
Study First Received: March 31, 2006
Last Updated: May 17, 2011
Health Authority: United States: Food and Drug Administration

Keywords provided by Johnson & Johnson Pharmaceutical Research & Development, L.L.C.:
Alzheimer's Disease
cardiac arrhythmias

Additional relevant MeSH terms:
Alzheimer Disease
Dementia
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Tauopathies
Neurodegenerative Diseases
Delirium, Dementia, Amnestic, Cognitive Disorders
Mental Disorders
Galantamine
Cholinesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Cholinergic Agents
Neurotransmitter Agents
Physiological Effects of Drugs
Parasympathomimetics
Autonomic Agents
Peripheral Nervous System Agents
Nootropic Agents
Central Nervous System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 18, 2014