Synonyms: Cromolyn sodium, Intal, Ibuprofen
Therapy Type: Small Molecule (timeline)
Target Type: Amyloid-Related (timeline), Inflammation (timeline)
Condition(s): Alzheimer's Disease
U.S. FDA Status: Alzheimer's Disease (Phase 3)
Company: AZTherapies, Inc.
ALZT-OP1 is a combination regimen of two FDA-approved drugs, cromolyn (designated ALZT OP1a) and ibuprofen (designated ALZT OP1b). In the ALZT-OP1 regimen, cromolyn is delivered via an oral, dry powder inhaler; ibuprofen is swallowed separately as an oral tablet.
Ibuprofen is a non-steroidal anti-inflammatory with an extensive history of preclinical and clinical evaluation in AD (see Ibuprofen). Widely used to treat asthma, cromolyn is a mast cell stabilizer that acts as an anti-inflammatory compound by suppressing cytokine release. This prescription drug has not been studied extensively in Alzheimer's research. One study conducted at Massachusetts General Hospital reported that cromolyn inhibits aggregation of Aβ monomers in vitro, and decreased soluble Aβ levels in the brain after peripheral administration in vivo (Hori et al., 2015). No other preclinical studies of cromolyn in AD, or the ALZT-OP1 combination in AD, are published in the peer-reviewed literature. For details on the proposed mechanism of action of this combination therapy, cromolyn delivery via the lungs, and preclinical treatment experiments, see patent WO 2014066318 A1.
In June and July 2015, AZTherapeutics compared two dosing regimens of ALZ-OP1, each lasting two days, in a Phase 1 plasma/CSF pharmacokinetic crossover study conducted with 26 healthy volunteers at Panax Clinical Research in Florida.
In September 2015, the company started an 18-month Phase 3 study. It is enrolling 600 people with early AD as verified by subjective memory complaint, impairment on a logical memory test, abnormally low CSF Aβ levels, and a CDR of 0.5. The trial will compare four groups: cromolyn active plus ibuprofen active, cromolyn active plus ibuprofen placebo, cromolyn placebo plus ibuprofen active, cromolyn placebo plus ibuprofen placebo. The primary outcome is change on the CDR-sum of boxes; the secondary outcomes are treatment-emergent adverse events. The study listing contains no additional outcome measures such as psychometric tests or biomarkers. Conducted mostly at commercial clinical trial sites in the United States, Australia, and Eastern European countries, this study aims for 100 completers per group and is set to run until 2018.
For all clinical trials on this combination therapy, see clinicaltrials.gov.
Clinical Trial Timeline
- Phase 3
- Study completed / Planned end date
- Planned end date unavailable
- Study aborted
- Hori Y, Takeda S, Cho H, Wegmann S, Shoup TM, Takahashi K, Irimia D, Elmaleh DR, Hyman BT, Hudry E. A Food and Drug Administration-approved asthma therapeutic agent impacts amyloid β in the brain in a transgenic model of Alzheimer disease. J Biol Chem. 2015 Jan 23;290(4):1966-78. Epub 2014 Dec 2 PubMed.
No Available Further Reading