Pilot Study Assessing the Effects of PXT00864 in Patients With Mild Alzheimer Disease (AD) (PLEODIAL-I)

First Single-blind Sequential Placebo-controlled Prospective Phase IIA Pilot Study Assessing the Effects of PXT00864 in Mild AD Patients

The purpose of this study is to assess the safety and efficacy on cognitive impairment and functioning of several doses of PXT00864 (new fixed combination of acamprosate and baclofen at low dose) in patients with mild Alzheimer Disease.

Study Overview

• Status: Completed
• Conditions: Alzheimer Disease
• Intervention / Treatment: Drug: placebo; Drug: PXT00864

• Study Type: Interventional
• Enrollment (Actual): 47
• Phase: Phase 2

Contacts and Locations

Study Locations

• France
  • Bordeaux, France
    • CMRR

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 60 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or female patients aged ≥ 60 years.
• Patient with a diagnosis of probable AD
• Progressive decline in cognition for more than six months which story is documented in patient medical records
• A Mini-Mental State Examination (MMSE) score of 20-26
• With a minimum of educational background
• Naïve to anti-dementia treatment
• MRI assessment which corroborates the clinical diagnosis (hippocampal atrophy) and excludes other potential causes of dementia especially cerebrovascular lesions
• If available, Cerebral Spinal Fluid (CSF) classical biomarkers should be at levels which corroborate the clinical diagnosis
• Ambulatory patient living at home with a caregiver available and living in the same household or interacting with the patient daily and available if necessary to ensure administration of the investigational product
• Absence of major or severe depressive disease
• Patient with a willingness to participate in this study and who have signed an informed consent form

Exclusion Criteria:

• Early onset of dementia, i.e. before 60 years old to avoid hereditary AD forms
• Significant neurological disease other than AD
• Major psychiatric disorder or syndrome (schizophrenia or bipolar disorder)
• Seizure disorders
• Other infectious, metabolic or systemic diseases affecting central nervous system
• Other active clinically significant illness
• Hospitalization or change of chronic concomitant medications one month prior to screening
• Patients with severe respiratory, hepatic or renal failure or with any other significantly potentially disabling abnormality detected during screening
• Known hypersensitivity to the tested treatment including active substance and excipients.
• Patients participating in another study and exposed to any investigational therapy within the 30 days prior to the entry in this study.
• Patient without medical care insurance

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NON_RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: TRIPLE

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: PXT00864 Dose 1; 1 orange capsule containing 0.4 mg of acamprosate , and 1 white capsule containing 6 mg of baclofen These 2 capsules are taken orally b.i.d. during 8 weeks.	Drug: PXT00864; PXT00864 is a fixed-dose combination of baclofen and acamprosate
EXPERIMENTAL: PXT00864 Dose 2; 1 orange capsule containing 1 mg of acamprosate , and 1 white capsule containing 15 mg of baclofen . These 2 capsules are taken orally b.i.d. during 8 weeks.	Drug: PXT00864; PXT00864 is a fixed-dose combination of baclofen and acamprosate
EXPERIMENTAL: PXT00864 Dose 3; 1 orange capsule containing 20 mg of acamprosate , and 1 white capsule containing 12 mg of baclofen . These 2 capsules are taken orally b.i.d. during 8 weeks.	Drug: PXT00864; PXT00864 is a fixed-dose combination of baclofen and acamprosate
PLACEBO_COMPARATOR: Placebo of PXT00864; 1 orange capsule containing placebo of acamprosate , and 1 white capsule containing placebo of baclofen . These 2 capsules are taken orally b.i.d. during 4 weeks	Drug: placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the total score of the 11-item Alzheimer´s Disease Assessment Scale- Cognitive Subscale (ADAS-Cog)	Scores on the ADAS-Cog range from 0-70 with higher scores indicating greater cognitive impairment.	Visit V0 (train), V1 (baseline), and every 4 weeks (visits V2, V3 and V4)
Number of Treatment Emergent Adverse Events (TEAEs)		throughout the 12-week study period.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the score of the Digit Symbol Substitution Test (DSST)	Scores on the DSST range from 0-93 with lower scores indicating greater impairment.	Visit V0 (train), V1 (baseline), and every 4 weeks (visits V2, V3 and V4)
Change From Baseline in the speed to perform the Zazzo's Cancellation Test		Visit V0 (train), V1 (baseline), and every 4 weeks (visits V2, V3 and V4)
Change From Baseline in the score of the Zazzo's Cancellation Test		Visit V0 (train), V1 (baseline), and every 4 weeks (visits V2, V3 and V4)
Change From Baseline in the score of the 15-second Isaacs Set Test		Visit V0 (train), V1 (baseline), and every 4 weeks (visits V2, V3 and V4)
Change From Baseline in the time score of the Trail Making Test - part A		Visit V0 (train), V1 (baseline), and every 4 weeks (visits V2, V3 and V4)
Change From Baseline in the time score of the Trail Making Test - part B		Visit V0 (train), V1 (baseline), and every 4 weeks (visits V2, V3 and V4)
Change From Baseline in the score of the Free and Cued Selective Reminding Test (FCSRT)	FCSRT is a memory test administered according to the procedure described by Gröber and Buschke modified with 16 verbal items.	1 (baseline) and V4 (end of study, after 12 weeks of treatment)
Change From Baseline in the score of the 4-item Instrumental Activities of Daily Living scale (IADL-PAQUID)	The 4-item Instrumental Activities of Daily Living scale (IADL) concerns four routine daily functions (using transportation, managing finances, using the phone and managing medicines use). Scores on the IADL range from 4-15 with higher scores indicating greater impairment.	V0 (train), V1 (baseline), and every 4 weeks (V2, V3 and V4)
Change From Baseline in the score of the Clinical Dementia Rating (CDR) scale	The Sum of Boxes score of the CDR ranges from 0 to 18, with higher scores indicating greater impairment.	1 (baseline) and V4 (end of study, after 12 weeks of treatment)
Change From Baseline in the score of the Apathy Inventory (AI) scale	Scores on the AI range from 0-12 with higher scores indicating greater impairment.	1 (baseline) and V4 (end of study, after 12 weeks of treatment)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change From Baseline in the cognitive Event Related Potential parameters (optional)	Some cognitive Event Related Potentials (ERP) with auditory oddball paradigm are performed as an ancillary study.	V1 (baseline), and every 4 weeks (V2, V3 and V4)

Collaborators and Investigators

• Sponsor: Pharnext SA
• Collaborators: Ascopharm Groupe Novasco

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (ACTUAL): June 1, 2015
• Study Completion (ACTUAL): June 1, 2015

Study Registration Dates

• First Submitted: December 19, 2014
• First Submitted That Met QC Criteria: February 6, 2015
• First Posted (ESTIMATE): February 11, 2015

Study Record Updates

• Last Update Posted (ESTIMATE): February 15, 2016
• Last Update Submitted That Met QC Criteria: February 12, 2016
• Last Verified: October 1, 2015

More Information

Terms related to this study

• Keywords: phase 2a; PXT00864; mild AD
• Additional Relevant MeSH Terms: Mental Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurocognitive Disorders; Neurodegenerative Diseases; Dementia; Tauopathies; Alzheimer Disease
• Other Study ID Numbers: CLN-PXT00864-03