Alzheimer's disease MedDRA version: 20.0 Level: LLT Classification code 10001896 Term: Alzheimer's disease System Organ Class: 100000004852
Conditions
Interventions
Product Name: pleconaril
Pharmaceutical Form: Capsule, hard
INN or Proposed INN: PLECONARIL
CAS Number: 153168-05-9
Current Sponsor code: APO-P001
Concentration unit: mg milligram(s)
Concentration typ
Sponsors
Apodemus Aktiebolag
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Male or female patients diagnosed with AD according to ICD-10 2) Age 60 to 85 years (inclusive) at the time of informed consent 3) Patient has stable AChEI and/or memantine for dementia (stable treatment is defined as stable in type of treatment and dose for at least 3 months prior to the baseline visit) 4) MMSE score 20 to 27 (inclusive) and judged by the Investigator to be able to give informed consent 5) Patients have adequate hearing, vision, and language skills to perform neuropsychiatric testing and interviews as specified in the protocol, as judged by the Investigator 6) 12-lead ECG with normal tracings; or changes that are not clinically significant and do not require medical intervention, as judged by the Investigator 7) Patient has a relative or caregiver, judged as reliable by the Investigator, who has signed informed consent. The relative or caregiver should participate in the patient’s visits at the clinic and assist the patient with drug compliance at home. 8) Willingness to participate after signing informed consent Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 25 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 95
Exclusion criteria
Exclusion criteria: 1) Active hepatitis B, active hepatitis C, or HIV infection 2) Serious cardiac disease including unstable or uncontrolled cardiac disease during the last 6 months and/or previous history of deep vein thrombosis or clinical signs of deep venous thrombosis 3) Major psychiatric disorder (e.g. schizophrenia or past or present major depression disorder or as judged by the investigator) 4) Major surgical procedure within 4 weeks prior to inclusion 5) Women of childbearing potential (WOCBP) without reliable contraceptive method. For the purpose of this trial, WOCBP includes any female who had experienced menarche, who had not undergone tubal ligation, and who is not postmenopausal. Post menopause was defined as amenorrhea = 12 consecutive months without another cause. 6) Previous stroke 7) Unstable treatment with Vitamin B12 medication, thyroid disorder medication, TNF-alpha blocking agents, antidepressants, cholinergic drugs, other AD medications (e.g. souvenaid) Unstable treatment is defined as unstable in type of treatment and dose in the 3 months prior to the baseline visit. (Therefore, all patients not requiring such treatment or with stable treatment may be included) 8) Participation in any other clinical trial within 30 days of inclusion (randomisation) in the trial or patients with unresolved investigational treatment-related adverse events 9) Other chronic disease or previous organ transplantation judged by the Investigator to interfere with the assessment of treatment success and/or ability to fully participate in the trial 10) Patients that require immunosuppressive treatments including azathioprine, ciclosporin, systemic steroid treatment (e.g. prednisolone at doses of =10 mg/day or hydrocortisone) or has received such treatment within the last 6 months prior to randomization 11) Patients that are treated with drugs that can interact significantly with Pleconaril; ethinylestradiol 12) Lack of suitability for participation in the trial, for any reason, as judged by the Investigator
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate the effect of Pleconaril on disease progression of Alzheimer’s Disease (AD) as assessed by the cognitive test Alzheimer’s Disease Assessment Scale-Cognitive Subscale (ADAS-cog) compared to placebo from baseline to 12 months (Visit 7);Secondary Objective: Secondary objectives To investigate: - the effect of Pleconaril on disease progression of AD assessed by the cognitive test – ADAS-cog, and the cognitive and functional test - Clinical Dementia Rating (CDR) compared to placebo from baseline to 3, 6, 9 and 18 months for ADAS-cog and 9, 12 and 18 months for CDR - the effect of Pleconaril on the number of patients with a clinically relevant change compared to placebo at 6, 9 and 12 months and at 10 weeks and 6 months follow up - the effect of Pleconaril on the disease progression of AD as assessed by the cognitive test - ADAS-cog and the cognitive and functional test - CDR after end of treatment with Pleconaril compared to baseline and 12 month visit respectively compared to placebo - the safety and tolerability of Pleconaril in patients with AD compared to placebo - the pharmacokinetics of Pleconaril in plasma from patients with AD;Primary end point(s): Change in ADAS-cog total score from baseline to 12 months (Visit 7);Timepoint(s) of evaluation of this end point: 12 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The efficacy endpoints are: Change in disease progression of AD as assessed by: - Change in ADAS-cog total score from baseline to 3 months (Visit 4), 6 months (Visit 5), 9 months (Visit 6), the 10 week follow up (Visit 8) and 6 month follow-up visit (Visit 9) - Change in CDR-sb from baseline to 9 months (Visit 6), 12 months (Visit 7) and 6 month follow-up visit (Visit 9) - Difference between groups in number of patients with a clinically relevant improvement and a clinically relevant worsening in ADAS-cog total score at 6 months (Visit 5), 9 months (Visit 6), 12 months (Visit 7) and at the 10 week and 6 month follow-up visits (visits 8 and 9). A clinically relevant improvement is defined as a decrease in ADAS-cog total score of at least 4 points compared to baseline and a clinically relevant worsening is defined as an increase in ADAS-cog total score of at least 4 points compared to baseline. - Change in ADAS-cog total score from 12 months (Visit 7) (end of treatment) to the 10 week and 6 month follow-up visits (visits 8 and 9) - Change in CDR-sb from 12 months (Visit 7) (end of treatment) to the 6 month follow-up visit (Visit 9) The safety endpoints are: - Frequency and intensity of AEs - Tolerability, as assessed by dose interruption (at least 5 consecutive days)- or discontinuation of Pleconaril /placebo - Changes in vital signs - Changes in laboratory parameters - Changes in physical examination - Signs of muscle inflammation and thrombosis - Changes in ECG - Changes in Weight The pharmacokinetic endpoints are: - Change of accumulation, as determined by trough concentrations (all patients) - Cmax following first daily dose on the first and last day of dosing (extended PK group) - Accumulation ratios, calculated from AUC(0-24) and Cmax, following the first daily dose on the first and last day of dosing (extended PK group) - If possible, apparent clearance (CL/F) and apparent volume of distribution (V/F), as determined | — |
Countries
Czech Republic, Poland
Contacts
Public ContactClinical trials
Apodemus Aktiebolag
Outcome results
None listed