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The purpose of this study is to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of multiple oral doses of DNL747 in subjects with Alzheimer's disease when administered for 29 days in a cross-over design
This is a Phase 1b randomized, placebo-controlled, double-blind, crossover study to evaluate the safety, tolerability, pharmacokinetics (PK), and pharmacodynamics (PD) of DNL747 in subjects with Alzheimer's disease (AD)
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| DNL747 First, Placebo Second | Experimental | Subjects will receive DNL747 for 29 days for the first period and then will switch to placebo for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods. |
|
| Placebo First, DNL747 Second | Experimental | Subjects will receive placebo for 29 days for the first period and then will switch to DNL747 for 29 days for the second period. There will be a 14-day washout period between the 2 treatment periods. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| DNL747 | Drug | DNL747 |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Subjects with Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | Randomization - Day 86 | |
| Number of Subjects with clinically significant neurological examination abnormalities | Randomization - Day 86 | |
| Number of Subjects with laboratory test abnormalities | Randomization - Day 86 |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic measure of maximum observed plasma concentration (Cmax) of DNL747 | Randomization - Day 86 | |
| Pharmacokinetic measure of time to reach maximum observed plasma concentration (Tmax) of DNL747 | Randomization - Day 86 |
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Key Inclusion Criteria:
Key Exclusion Criteria:
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Clinical Site(s) | Miami | Florida | 33143 | United States | ||
| Clinical Site(s) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 35649245 | Derived | Vissers MFJM, Heuberger JAAC, Groeneveld GJ, Oude Nijhuis J, De Deyn PP, Hadi S, Harris J, Tsai RM, Cruz-Herranz A, Huang F, Tong V, Erickson R, Zhu Y, Scearce-Levie K, Hsiao-Nakamoto J, Tang X, Chang M, Fox BM, Estrada AA, Pomponio RJ, Alonso-Alonso M, Zilberstein M, Atassi N, Troyer MD, Ho C. Safety, pharmacokinetics and target engagement of novel RIPK1 inhibitor SAR443060 (DNL747) for neurodegenerative disorders: Randomized, placebo-controlled, double-blind phase I/Ib studies in healthy subjects and patients. Clin Transl Sci. 2022 Aug;15(8):2010-2023. doi: 10.1111/cts.13317. Epub 2022 Jun 1. |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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| Placebo |
| Drug |
Placebo |
|
| Pharmacokinetic measure of area under the plasma drug concentration-time curve (AUC) of DNL747 | Randomization - Day 86 |
| Pharmacokinetic terminal disposition rate constant (λz) with the respective t1/2 of DNL747 | Randomization - Day 86 |
| Pharmacokinetic measure of CSF concentrations of DNL747 | Randomization - Day 86 |
| Pharmacodynamic measure of pS166 in PBMCs | Randomization - Day 86 |
| Orlando |
| Florida |
| 32806 |
| United States |
| Clinical Site(s) | Dallas | Texas | 75231 | United States |
| Clinical Site(s) | Salt Lake City | Utah | 84124 | United States |
| Clinical Site(s) | Groningen | 9713 | Netherlands |
| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |