A Study of RO4602522 in Patients With Alzheimer Disease and in Healthy Volunteers

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01701089
First received: September 27, 2012
Last updated: August 26, 2014
Last verified: August 2014
  Purpose

This open-label, multiple dose, parallel group study will assess the monoamine o xidase in the brain by in vivo positron emission tomography (PET) and safety of RO4602522 in patients with Alzheimer disease and in healthy volunteers. Patients and volunteers will receive multiple doses of RO4602522 and up to three injecti ons of C11-L-deprenyl-D2 used in the PET.


Condition Intervention Phase
Alzheimer Disease, Healthy Volunteer
Drug: 11C-L-deprenyl-D2
Drug: RO4602522
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Pharmacokinetics/Dynamics Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: An Open-Label, Parallel Group Study to Assess the Inhibition of Brain MAO-B by RO4602522 After Repeated Dosing in Patients With Alzheimer's Disease and in Healthy Control Subjects

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Change in monoamine oxidase (MAO-B) enzyme activity as measured by in vivo positron emission tomography (PET) [ Time Frame: Days 1, 14, and between days 15 and 34 ] [ Designated as safety issue: No ]
  • Pharmacokinetics: Plasma concentration of RO4602522 [ Time Frame: Days 1, 8, 14, and between Days 15 and 34 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Reduction of 11C-L-deprenyl-D2 tracer uptake by in vivo positron emission tomography (PET) [ Time Frame: Days 1, 14, and between days 15 and 34 ] [ Designated as safety issue: No ]
  • Safety: incidence of adverse events [ Time Frame: 35 days ] [ Designated as safety issue: No ]

Enrollment: 17
Study Start Date: September 2012
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: RO4602522 Group 1 Drug: 11C-L-deprenyl-D2
Intravenous injection of 11C-L-deprenyl-D2 before positron emission tomography (PET); up to 3 injections in total
Drug: RO4602522
Multiple doses of RO4602522 for 14 days
Experimental: RO4602522 Group 2 Drug: 11C-L-deprenyl-D2
Intravenous injection of 11C-L-deprenyl-D2 before positron emission tomography (PET); up to 3 injections in total
Drug: RO4602522
Multiple doses of RO4602522 for up to 17 days

  Eligibility

Ages Eligible for Study:   50 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

General:

  • Adults between 50-80 years of age. Females must be of non-child-bearing potential or if of child-bearing potential must use an acceptable form of contraception
  • Body mass index (BMI) 18.0-32.0 kg/m2 inclusive

Healthy volunteers:

  • Healthy, with no clinically relevant finding on physical examination at screening and Day -1
  • No suspicion of cognitive impairment/early dementia from neuropsychological battery as judged by the investigator
  • Able to participate and willing to give informed consent, and comply with the study restrictions.

Alzheimer Disease (AD) patients:

  • Probable Alzheimer's disease, based on the National Institute of Neurological and Communicative
  • Disorders and Stroke (NINCDS/ADRDA) and DSM-IV criteria
  • Have a MMSE score at screening between 17 and 26 inclusive
  • Modified Hachinski Ischemia Scale score of </=4
  • A neuroimaging evaluation of the brain by MRI which supports a diagnosis of AD, with no evidence of focal disease to account for dementia or MRI exclusion criteria
  • Medications taken for symptomatic treatment of AD must be maintained on a stable dosage regimen for at least 1 month before Day 1.
  • Able to participate in all scheduled evaluations
  • The patient has an appropriate caregiver or community dwelling with caregiver capable of accompanying subject on all visits to the center as judged by the investigator.
  • In the opinion of the investigator the patient and caregiver will be compliant and have a high probability of completing the study.
  • Signed and dated written informed consent obtained from the patient, co-signed by the patient's closest relatives and legally authorized representative, as required by national law for patients that are incapable of giving informed consent.

Exclusion Criteria:

General:

  • Any active disease of the gastrointestinal (GI) system, liver, or kidneys that could result in altered absorption, excess accumulation, or impaired metabolism or excretion of drugs, including a history of major upper or middle GI tract surgery or current significant chronic disease of the GI tract
  • Clinically relevant abnormal history, physical findings, ECG, or laboratory values at the screening assessment
  • History of cancer in the past five years, except for fully treated local basal carcinoma, or fully treated carcinoma in situ of cervix
  • Any major illness occurring within 1 month prior to the screening examination or febrile illness within 5 days prior to first dose
  • History of psychotropic medicine abuse
  • At risk of suicide in the opinion of the investigator or having a Yes to question number 4 or 5 of the Suicidal Ideation section of the C-SSRS
  • Administration of ionizing radiation or radioisotope for research, diagnostics test or therapy within 12 months prior to the present study which would exceed the local yearly radiation dose exposures for participation in research studies (except for dental x-rays, minimal plain films such as chest and ankle X-rays) or subjects who regularly work with ionizing radiation or radioactive material.
  • Participation in a clinical study with an investigational drug within 3 months before screening
  • Positive test for hepatitis B, hepatitis C, or HIV at screening
  • Loss or donation of more than 450 mL blood in the 4 months before screening or donation of plasma within 14 days of screening.
  • History of drug abuse or evidence of drug abuse in urine test performed at screening
  • Current alcohol abuse, or regular intake of more than 2 units of alcohol daily
  • Coffee (or tea) consumption > 5 cups per day or xanthine containing drinks >/1.5 liter/day

Healthy volunteers:

  • Family history of Alzheimer's disease in 1st and 2nd degree relative under 75 years.
  • Evidence or history of clinically significant neurological or psychiatric disorders.

AD Patients:

  • Any neurological or psychiatric condition not specified in exceptions
  • Previous immunization therapy for AD
  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: NCT01701089

Locations
Sweden
Stockholm, Sweden, 141 86
Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

No publications provided

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01701089     History of Changes
Other Study ID Numbers: BP28253
Study First Received: September 27, 2012
Last Updated: August 26, 2014
Health Authority: Sweden: Medical Product Agency

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
Selegiline
Antiparkinson Agents
Anti-Dyskinesia Agents
Central Nervous System Agents
Therapeutic Uses
Pharmacologic Actions
Monoamine Oxidase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on August 26, 2014