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

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.