Clinical trial NCT02482324: Phase 1 Study of ALZT-OP1 Combination Therapy in Normal Healthy Volunteers
Official title: A Phase I, Randomized, Open-Labeled Pharmacokinetic Study of ALZT-OP1 in Normal Healthy Volunteers
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy Volunteers
Lead sponsor: AZTherapies, Inc.
Sponsor class: INDUSTRY
Collaborators: name: Panax Clinical Research
name: Pharma Consulting Group AB
name: KCAS
First posted: 2015-06-26
Enrollment: 26
Sex: ALL
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: This is an open-labeled, cross-over design, pharmacokinetic study, to determine the pharmacokinetics of ALZT-OP1 (a combination drug therapy) designated as ALZT-OP1a and ALZT-OP1b, in both plasma and CSF, following co-administration of the active compounds, in healthy volunteers, aged 55-75, and in good general health.

Detailed description: This is an open-labeled, cross-over design, pharmacokinetic study, where 24 subjects will be randomly assigned to receive treatment regimen A-B or B-A on two consecutive days of dosing.

Two dosing groups are planned for the study :

* Group 1 (n=12)
* Group 2 (n=12)

Each group will be admitted to the Phase I Unit the evening before dosing and will initiate dosing the next morning for 2-days of consecutive treatment (A-B, or B-A). Both groups will undergo identical study related procedures, except those subjects that consent to CSF collection on Day 1 of dosing.

Dose regimen A consists of a single inhaled oral dose of ALZT-OP1a via dry powder inhaler + a single oral tablet dose of ALZT-OP1b.

Dose regimen B consists of two oral inhaled doses of ALZT-OP1a, not more than 2 minutes apart, via dry powder inhaler + two oral tablet doses of ALZT-OP1b.

Plasma Collection, All Subjects (n=24) 1 mL blood samples will be collected at T: 0, 5, 10, 15, 30, 1 hr, 2 hr, 4 hr, and 6 hours, following ALZT-OP1 administration (Days 1 and 2).

CSF Collection, Sub-group (n=12) A sub-group of 12 subjects will be consented for CSF collection.

1 mL of CSF will be collected at T: 0, 5 min, 30 min, 2 hr, and 4 hours, following ALZT-OP1 administration (Day 1 only).

Eligibility criteria: Inclusion Criteria:

* Provide a signed written informed consent;
* Age 55-75 inclusive;
* ECG within normal limits;
* Body mass index (BMI) ≥ 18 kg/m2 and ≤ 30 kg/m2;
* Negative urine drug screen for selected drugs of abuse at screening;
* Negative for hepatitis and HIV at screening;
* Good general health, as determined by medical history, physical examination, and clinical laboratory testing;
* Willingness to stay in the unit overnight for the duration of the study;
* Consent for CSF collection (for those in CSF group).

Exclusion Criteria:

* Current smokers, or ex-smokers with a remote history (\> 100 pack/year);
* Clinically significant medical conditions;
* History of ECG abnormalities;
* Symptomatic viral infection, or suspicion thereof (including rhinitis) in the last 14 days prior to dosing;
* Signs of active pulmonary infection or other pulmonary inflammatory conditions, even in absence of febrile episodes, in the last 14 days;
* History or presence of disease in the kidneys and/or heart, lungs, liver, gastrointestinal tract, endocrine organs or other conditions such as metabolic disease known to interfere with the absorption, distribution, metabolism, and excretion of drugs;
* Malignancy, regardless of location;
* Autoimmune disorders such as (but not limited to) lupus erythematosus, multiple sclerosis, rheumatoid arthritis, or sarcoidosis;
* Investigational agents are prohibited one month prior to entry and for the duration of the trial;
* Currently taking medications known to be CYP2C9 inducers (i.e. carbamazepine and rifampicin);
* Currently taking cromolyn, or have taken cromolyn, within the past 30 days;
* NSAID use (products containing ibuprofen while on study);
* Aspirin, or products containing aspirin, while on study;
* Allergy or hypersensitivity to cromolyn (also known as Intal®, Nasalcrom®, etc.);
* Allergy or hypersensitivity to ibuprofen (Advil®, Motrin®, Nuprin®, etc.) or aspirin, including Stevens-Johnson syndrome;
* History of hypersensitivity or allergies to any of the drug compound under investigation (cromolyn, ibuprofen, lactose, or magnesium stearate);
* History of clinically significant respiratory disorders and chronic respiratory disease with impaired respiratory effort or difficulty taking inhaled drugs (examples: COPD, emphysema);
* Abnormal pulmonary function test, defined for this protocol as: FEV1/FVC \< 70% of the predicted value for the subject, when compared to reference values; AND FEV1 and FVC \< 70% of predicted value when compared to reference values, indicating moderate to severe respiratory obstruction;
* Any other disease or condition, which, in the opinion of the investigator, would make the subject unsuitable for this study;
* Female subjects of reproductive potential with a positive pregnancy test (urine or serum) or who are pregnant or lactating.

Primary outcomes:
measure: Non-compartmental plasma pharmacokinetics for ALZT-OP1a and ALZT-OP1b
timeFrame: T=0 to 6 hours (0, 5, 10, 15, 30, 60, 120, 240, and 360 minutes)
Secondary outcomes:
measure: Levels of ALZT-OP1a and ALZT-OP1b in cerebrospinal fluid (CSF)
timeFrame: T=0 to 4 hours (0, 5, 30, 120, and 240 minutes)
measure: Number of Treatment Emergent Adverse Events (TEAE)
timeFrame: 2 days
Other outcomes:
Locations:
city: Miami Lakes
country: United States
facility: Panax Clinical Research
state: Florida
Study officials:
affiliation: Study Sponsor
name: David Elmaleh, PhD
role: STUDY_CHAIR
affiliation: Study Sponsor
name: David Brazier, BS
role: STUDY_DIRECTOR
References: