Randomized I/II Phase Study of ALZT-OP1 Combination Therapy in Alzheimer's Disease and Normal Healthy Volunteers

NCT04570644 | Completed Phase 1 FDA Drug

• 1 other identifier: AZT-008
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, open-label, cross-over, pharmacokinetic and pharmacodynamic PK/PD study. (Part A)The PK portion of the study is designed to evaluate 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 two active investigational products, in healthy volunteers and Alzheimer subjects aged 55-79 and in good health. (Part B) The PD portion of the study will evaluate the pharmacodynamics of ALZT- OP1, using both plasma and CSF biomarkers, following 60 days of consecutive daily treatment, in AD subjects only.

Conditions

Healthy Volunteers; Alzheimer Disease

Outcome Measures

Primary Outcomes (9)

• Part A Non-compartmental PK parameters will be calculated and reported for ALZT-OP1a and ALZT-OP1b

  • PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF

  • 2 Days

• PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF AUC 0-∞

  Evaluation AUC 0-∞ (area under the curve from 0 to infinity)

  2 Days

• PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF AUC 0-t

  Evaluation AUC 0-t (area under the curve from 0 to t hours where t is the last measured concentration)

  2 Days

• PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF AUCPLASMA/AUCCSF

  Evaluation AUCPLASMA/AUCCSF (ratio at 60 min, 120 min, 240 min, 360 min and 480 min)

  2 Days

• PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF CL/F

  Evaluation CL/F (apparent total body clearance)

  2 Days

• PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF Cmax

  Evaluation Cmax (maximum plasma and CSF concentration observed)

  2 Days

• PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF t½ (half-life)

  Evaluation t½ (half-life)

  2 Days

• PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF tmax

  Evaluation tmax (sampling time at which Cmax occurred)

  2 Days

• PK profile for ALZT-OP1a and ALZT-OP1b in plasma and CSF Vd/F

  Evaluation Vd/F (apparent volume of distribution)

  2 Days

Secondary Outcomes (13)

• Biomarker Beta Amyloid (Αβ-42) Sample Analysis plasma and CSF Day 1 to 60 Days

  Day 1 to Day 60

• Biomarker Beta Amyloid (Αβ-40) Sample Analysis plasma and CSF Day 1 to 60 Days

  Day 1 to Day 60

• Biomarker Beta Amyloid (Αβ-38) Sample Analysis plasma and CSF Day 1 to 60 Days

  Day 1 to Day 60

• Biomarker Total Tau Sample Analysis plasma and CSF Day 1 to 60 Days

  Day 1 to Day 60

• Biomarker Neurofilament light (Nf-L) Sample Analysis plasma and CSF Day 1 to 60 Days

  Day 1 to Day 60

Other Outcomes (1)

• Number of Treatment Emergent Adverse Events (TEAE)

  2 Days Part A and 60Days Part B

Study Arms (2)

Part A

OTHER

24 subjects randomized to receive treatment: (A-B) = Single 17.1 mg oral inhaled dose of ALZT-OP1a (cromolyn) via dry powder inhaler and a single oral 10 mg tablet of ALZT-OP1b (ibuprofen) on Day 1. On Day 2, subjects would receive two 17.1 mg doses of ALZT-OP1a via dry powder inhaler and two 10 mg tablets of ALZT-OP1b (ibuprofen), within two minutes of each other. (B-A) = Two 17.1 mg doses of ALZT-OP1a (cromolyn) and two doses of 10 mg ALZT-OP1b (ibuprofen) on Day 1 and single 17.1 mg dose of ALZT-OP1a cromolyn 17.1 mg and a single 10 mg dose of ALZT-OP1b (ibuprofen) on Day 2. All subjects will have plasma and CSF collected for PK analysis.

Drug: ALZT-OP1 (cromolyn and ibuprofen) ALZT-OP1a (cromolyn) and ALZT-OP1b (ibuprofen)

Part B

OTHER

PD - 32 subjects (AD only) will be enrolled in the PD portion of the study. Twenty-four (24) subjects will be assigned to Treatment Group 1 to receive a single (17.1 mg) inhaled dose of ALZT-OP1a (cromolyn) plus a single (10 mg) oral dose of ALZT-OP1b (ibuprofen) daily for 60 days. All subjects will have plasma and CSF collected for PD biomarker analysis. Eight (8) A subjects will be assigned to Treatment Group 2 (Control Group) and will not be administered study drug.

Drug: ALZT-OP1 (cromolyn and ibuprofen) ALZT-OP1a (cromolyn) and ALZT-OP1b (ibuprofen)

Interventions

ALZT-OP1 (cromolyn and ibuprofen) ALZT-OP1a (cromolyn) and ALZT-OP1b (ibuprofen) DRUG

Drug : ALZT-OP1a 1. Mast cell stabilizer 2. Neuroinflammatory microglial modulator ALZT-OP1b anti-inflammatory Device: Dry Powder Inhaler The inhaler will be used to deliver ALZT-OP1a via oral inhalation for dosing on study.

Also known as: Cromolyn, Intal, Cromolyn Sodium, Sodium cromoglycate, Ibuprofen

Part A; Part B

Eligibility Criteria

• Age: 55 Years - 79 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• For All Subjects
• Provide a signed written informed consent;
• Age 55-79 old (inclusive);
• ECG without abnormal, clinically significant findings;
• 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;
• Negative for COVID-19 at screening;
• Good general health, as determined by medical history, physical examination, and clinical laboratory testing;
• Must provide written informed consent for CSF sampling. For AD Subjects Only
• Diagnosed with mild to moderate Alzheimer's disease;
• Clinical Dementia Rating (Global) 0.5
• Mini-mental state examination (MMSE) ≤ 22;
• Must be fluent in the language of the cognitive testing material being administered;
• Stability of permitted medications for 4 weeks prior to study start;

You may not qualify if:

• For All Subjects
• Current smokers, or ex-smokers with a remote history (\> 100 pack/year);
• Clinically significant medical conditions;
• History of abnormal clinically significant 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 (e.g., carbamazepine and rifampicin;
• Currently taking cromolyn, or have taken cromolyn products, within the past 30 days;
• Non-steroidal anti-inflammatory drug (NSAID) use (products containing ibuprofen while on study);
• Allergy or hypersensitivity to cromolyn (also known as Intal®, Nasalcrom®, Opticrom®, Gastrocrom®, etc.);
• Allergy or hypersensitivity to ibuprofen (Advil®, Motrin®, Nuprin®, etc.) or aspirin, including Stevens-Johnson syndrome;

Sponsors & Collaborators

• AZTherapies, Inc.: lead

Study Sites (1)

Panax Clinical Research

Miami Lakes, Florida, 33014, United States

Location

Related Links

• Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Elderly Volunteers

MeSH Terms

Conditions

Alzheimer Disease

Interventions

Cromolyn Sodium; Ibuprofen

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Chromones; Benzopyrans; Pyrans; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals

Study Officials

• David R. Elmaleh, PhD

  AZTherapies, Inc.

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: A Phase I/ II Randomized, Open-Label Study to Evaluate Pharmacokinetic and Pharmacodynamic Effects and Safety of ALZT-OP1 (co-administration of ALZT-OP1a and ALZT-OP1b) in Subjects with Alzheimer's Disease and Normal Healthy Volunteers
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Model Details: ALZT-OP1a (cromolyn) and ALZT-OP1b (Ibuprofen) are being evaluated in this study.

Study Record Dates

• First Submitted: September 17, 2020
• First Posted: September 30, 2020
• Study Start: August 28, 2020
• Primary Completion: January 18, 2021
• Study Completion: January 18, 2021
• Last Updated: March 3, 2022

Record last verified: 2020-09

Locations

US (1)