Randomized I/II Phase Study of ALZT-OP1 Combination Therapy in Alzheimer's Disease and Normal Healthy Volunteers
Condition: Healthy Volunteers; Alzheimer Disease
MeSH terms: Alzheimer Disease
Study type: Interventional
Phase: Phase 1

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.
    

Detailed description: 
      This is a phase I/II randomized, open-label, cross-over, PK/PD study. The PK (Part A) portion
      of the study is designed to evaluate both single and double doses of ALZT-OP-1a (17.1mg or
      34.2 mg) and ALZT-OP1b (10 mg or 20 mg) in both Alzheimer's subjects and healthy volunteers.
      The PD (Part B) portion of the study is designed to evaluate single doses of ALZT-OP-1a
      (17.1mg) and ALZT-OP1b (10 mg) in AD subjects treated for 60 days. An Alzheimer's control
      group will be utilized for comparison to active treatment groups but will not be administered
      study treatment; however, they will have biomarkers collected.

      PK (Part A) n=24, both healthy volunteers and AD subjects

      Part A is an open-label study, cross-over, PK study where 24 subjects will be randomly
      assigned to receive treatment regimen A-B or B-A for two consecutive day of dosing.

      Subjects will be admitted to the Phase 1 unit the morning before dosing and will initiate
      dosing the following morning for 2 consecutive days of dosing (A-B, or B-A).

      Day 1 (A-B) will consist of a single inhaled oral dose of ALZT-OP1a via dry powder inhaler +
      a single oral tablet dose of ALZT-OP1b.

      Day 2 (B-A) will consist of two oral inhaled doses of ALZT-OP1a, not more than 2 mins apart,
      via dry powder inhaler + two oral tablets doses of ALZT-OP1b.

      Day 1 (B-A) will consist of two oral inhaled doses of ALZT-OP1a, not more than 2 mins apart,
      via dry powder inhaler + two oral tablets doses of ALZT-OP1b.

      Day 2 (A-B) regimen consists of a single inhaled oral dose of ALZT-OP1a via dry powder
      inhaler + a single oral tablet dose of ALZT-OP1b.

      AD subjects will be given the option to roll over into the PD portion of the study.

      PD (Part B) n=32, AD subjects only

      Part B is an open-label, PD study where 32 AD subjects will be randomly assigned to receive
      either active treatment or be assigned to a non-treatment control arm.

      Twenty-four (24) subjects will be randomly assigned to Treatment Group 1 to receive a single
      (17.1 mg) inhaled dose of ALZT-OP1a plus a single (10 mg) oral dose of ALZT-OP1b daily for 60
      days.

      Eight (8) subjects will be randomly assigned to Treatment Group 2 (Control Group) and will
      not be administered study drug.

      All subjects will have plasma collected on Day 1, Day 30, and Day 60 and CSF collected on Day
      1 and Day 60.
    

Intervention name(s): ALZT-OP1 (cromolyn and ibuprofen) ALZT-OP1a (cromolyn) and ALZT-OP1b (ibuprofen)
Intervention type(s): Drug
Intervention description(s): Drug : ALZT-OP1a
Mast cell stabilizer
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.
Other intervention name(s): Cromolyn, Intal, Cromolyn Sodium, Sodium cromoglycate; Ibuprofen
Intervention MeSH terms: Cromolyn Sodium; Ibuprofen
Allocation: Randomized
Intervention model: Crossover Assignment
Intervention model description: ALZT-OP1a (cromolyn) and ALZT-OP1b (Ibuprofen) are being evaluated in this study.
Masking: None (Open Label)
Primary purpose: Treatment