A phase III Safety and Efficacy Study of ALZT-OP1 in Subjects with Evidence of Early Alzheimer’s Disease.

Phase 1

Conditions: Early stage of Alzheimer's Disease.
MedDRA version: 20.0Level: LLTClassification code 10001896Term: Alzheimer's diseaseSystem Organ Class: 100000004852
Therapeutic area: Psychiatry and Psychology [F] - Mental Disorders [F03]

Registration Number: EUCTR2015-002147-34-BG

Lead Sponsor: AZTherapies, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: ot Recruiting

Sex: All

Target Recruitment: 600

Inclusion Criteria

1. 55-79 years old (inclusive);
2. = 8 years of education (any type of schooling);
3. Study partner is available who has frequent contact with the participant (e.g. an average of 10 hours per week or more), and can accompany the participant to all clinic visits for the duration of the protocol;
4. Evidence of early AD, as defined by all of the following:
a. Memory complaint by subject or study partner that is verified by a study partner;
b. Objective memory impairment for age, documented by scoring below the
education adjusted cutoff of the Logical Memory II subscale (Delayed Paragraph
Recall) from the Wechsler Memory Scale Third Edition (the maximum score is 25):
i. = 8 for 16 or more years of education, or
ii. = 4 for 8-15 years of education;
c. Essentially preserved general cognitive function;
d. Largely intact functional activities;
e. Not demented;
5. Cerebrospinal fluid (CSF) biomarker results consistent with early AD, including CSF Aß-42 levels = 180 pg/mL and = 690 pg/mL;
6. Clinical Dementia Rating (Global) = 0.5; Memory Box Score must be at least 0.5;
7. Must be fluent in the language of the cognitive testing material being administered;
8. Stability of permitted medications for 4 weeks prior to study entry; subjects receiving acetylcholinesterase inhibitors and/or memantine should be on stable dose of those medications for at least 12 weeks prior to study start with every effort to maintain stable dose for duration of study;
9. Visual and auditory acuity adequate for neuropsychological testing;
10. Good general health with no diseases expected to interfere with the study;
11. Must provide written informed consent for APOe4 genotype testing;
12. Must provide written informed consent for CSF sampling.
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 200
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 400

Exclusion Criteria

1. Any significant neurological disease other than suspected incipient AD, such as Parkinson’s disease, multi-infarct dementia, Huntington’s disease, normal pressure hydrocephalus, brain tumor, progressive supranuclear palsy, seizure disorder,subdural hematoma, multiple sclerosis, or history of significant head trauma followed by persistent neurologic defaults or known structural brain abnormalities;
2. Major depressive episode, as described in the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) within the past 1 year, which could lead to difficulty complying with the protocol);
3. History of schizophrenia or bipolar disorder (DSM-IV criteria);
4. History of alcohol or substance abuse or dependence within the past 3 years (DSM-IVcriteria);
5. Currently taking medications that could lead to difficulty complying with the protocol;
subjects must be on a stable dose of current medications for 4 weeks prior to study entry; with the exception of acetylcholinesterase inhibitors and/or memantine, which must be on stable dose for at least 12 weeks prior to study entry;
6. Investigational agents are prohibited one month prior to entry and for the duration of the trial;
7. Currently taking medications known to be CYP2C9 inducers (i.e. carbamazepine and rifampicin);
8. Currently taking cromolyn, or have taken cromolyn, within the past 12 months;
9. Chronic daily use of high-dose NSAID for osteoarthritis, rheumatoid arthritis, or other chronic inflammatory diseases (chronic” defined as 3200 mg/day for > two weeks);
10. Chronic daily use of aspirin exceeding standard of care guidelines for low dose aspirin therapy for prevention of strokeand/or other recommended uses;
11. Allergy to cromolyn (also known as Intal®, Nasalcrom®, Opticrom®, Gastrocrom®,etc.);
12. Allergies to ibuprofen (Advil®, Motrin®, Nuprin®, etc.) or aspirin, including Stevens-Johnson syndrome;
13. Clinically significant respiratory disorders with impaired respiratory effort or difficulty taking inhaled drugs; (examples: Stage III-IV COPD, emphysema);
14. Uncontrolled chronic asthma;
15. Abnormal pulmonary function test, defined for this protocol as: FEV1/FVC <
predicted value for subject AND FEV1 < 70% of predicted value, indicating moderate or severe respiratory obstruction;
16. Taking inhaled protein products on a chronic basis (such as insulin, PTH, etc.)
17. Any significant systemic illness or unstable medical condition which could lead to difficulty complying with the protocol;
18. Pregnancy or lactation for female subjects of child-bearing potential (i.e., < two years post-menopausal or not surgically sterile)
19. For sexually active male subjects, unwillingness or incapability of using appropriate contraception methods;
20. Severe renal or hepatic impairment.

Study & Design

Study Type: Interventional clinical trial of medicinal product

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the safety and tolerability of a combination treatment regimen (ALZT OP1)of oral inhaled cromolyn, plus oral ibuprofen tablets, compared to each of the single component groups.<br>To determine whether this combination treatment regimen slows down, arrests or reverses cognitive and functional decline in subjects with evidence of early AD.;Secondary Objective: Not applicable;Primary end point(s): The primary endpoint is the difference in performance in the<br>ALZT-OP1 combination treatment group compared to each of<br>the single component groups, as quantified by the mean<br>change from baseline to week 72 in points scored on the<br>Clinical Dementia Rating-Sum of Boxes (CDR-SB).<br>The primary efficacy variable is change in CDR-SB from<br>baseline during the study.;Timepoint(s) of evaluation of this end point: 72 weeks

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): not applicable;Timepoint(s) of evaluation of this end point: not applicable

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