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Study interrupted by COVID-19 pandemic and could not be restarted at current location. Study investigators determined that relocating and continuing the study under its original scope was not feasible given preliminary results from IM injections.
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| Name | Class |
|---|---|
| University of Southern California | OTHER |
| Alzheimer's Association | OTHER |
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The purpose of this study is to identifying the intramuscular dose equivalent to the 4mg intravenous dose and assess its safety and tolerability as a weekly injection.
The purpose of this bridging study is to advance the therapeutic development of Allopregnanolone (Allo) by using the intramuscular (IM) route of administration as an alternative to the intravenous (IV) route. In order to identify the equivalent IM dose we will conduct pharmacokinetic (PK) analysis previously informed by simulations and modeling. We will recruit a total of 12 participants, both males and females equally distributed, into this single-arm, open-label study.
PK analysis and dose finding will take place for the initial 4 weeks; some participants may not require all 4 weeks of initial dosing to establish maintenance dose. Once maintenance dose is established all participants will receive weekly administration of Allo IM until they complete 12 weeks total of Allo exposure (5 or 6 clinic visits and 6 or 7 home-nurse visits).
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Allo IM cohort | Experimental | Allopregnanolone 4-18mg IM, weekly, for 12 weeks. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Allopregnanolone | Drug | Administration of weekly IM injections of Allopregnanolone. |
|
| Measure | Description | Time Frame |
|---|---|---|
| Safety - Adverse events | Incidence and severity of treatment emergent adverse events assessed weekly. | From baseline to visit 16 (14 weeks) |
| Safety - clinical laboratory measures | Proportion of subjects exceeding pre-established critical laboratory values. | From Baseline to visit 16 (14 weeks) |
| Safety - clinical assessment | Proportion of subjects with abnormal findings in physical/neurological exams, vital signs and electrocardiograms. | From Baseline to visit 16 (14 weeks) |
| Measure | Description | Time Frame |
|---|---|---|
| Pharmacokinetic parameter - Cmax | Determine maximum serum concentration of Allo after IM administration of each dose. | Visits 3 - 6 (up to 4 weeks) |
| Pharmacokinetic parameter - AUC | Determine the area under the curve after each IM administration of Allo. |
| Measure | Description | Time Frame |
|---|---|---|
| MRI brain volumes | To evaluate MRI-based brain volumes 1-week before before and 1-week after the administration of Allo IM for 12 weeks (total assessment period of 14 weeks). | Baseline to visit 16 (14 weeks) |
| Cambridge Neuropsychological Test Automated Battery (CANTAB) Paired Associates Learning (PAL) |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Roberta D Brinton, PhD | University of Arizona | Principal Investigator |
| Lon S Schneider, MD, MS | University of Southern California | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II | Los Angeles | California | 90033 | United States |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| D060825 | Cognitive Dysfunction |
| D003704 | Dementia |
| ID | Term |
|---|---|
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
| D024801 | Tauopathies |
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| ID | Term |
|---|---|
| D011280 | Pregnanolone |
| ID | Term |
|---|---|
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
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Single-arm, open-label study
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| Visits 3 - 6 (up to 4 weeks) |
| Pharmacokinetic parameter - Tmax | Determine the time at which Cmax is attained. | Visits 3 - 6 (up to 4 weeks) |
| Pharmacokinetic parameter - Clearance | Pharmacokinetic measurement of the volume of plasma from which Allo is completely removed per unit time. | Visits 3 - 6 (up to 4 weeks) |
| Pharmacokinetic parameter - Volume of distribution | Determine the volume of distribution at steady state of Allo. | Visits 3 - 6 (up to 4 weeks) |
| Satisfaction and feasibility of home nurse survey | Standardized patient satisfaction questionnaire to assess the feasibility of home-health care visits to administer the study medication and its desirability by participants and caregivers. Levels of satisfaction measured on a 5-point scale (1 = lowest satisfaction, 5 = greatest). | Visits 8-9 and 11-15 (up to 8 weeks) |
Test to evaluate changes in cognition |
| Baseline to visit 16 (14 weeks) |
| Mini-Mental State Exam (MMSE) | Test to evaluate changes in cognition. | Baseline to visit 16 (14 weeks) |
| Alzheimer's Disease Assessment Scale Cognitive Subscale 14 (ADAS-Cog14) | Well known test to evaluate changes in cognition. Scores on this 14 item test range from 0 (best) to 85 (worse); a positive change indicates cognitive worsening. | Baseline to visit 16 (14 weeks) |
| Clinical Dementia Rating Scale Sum of Boxes (CDR-SB) | Clinical scale that rates the severity of dementia as absent, questionable, mild, moderate, or severe (CDR score of 0, 0.5, 1, 2, or 3, respectively). | Baseline to visit 16 (14 weeks) |
| Cogstate Alzheimer's battery | Test to evaluate changes in cognition. | Baseline to visit 16 (14 weeks) |
| Activities of daily living | To assess activities of daily living per the Alzheimer's Disease Cooperative Study - Activities of Daily Living Scale (ADCS-iADLS). In a structured interview format, informants are queried as to whether participants attempted each item in the inventory during the prior 4 weeks and their level of performance. Scores range from 0-56. | Baseline to visit 16 (14 weeks) |
| Caregiver burden survey | Assessed per Zarit's burden 22-item questionnaire. Burden measured on a 5-point scale (0 = never burdened, 4 = nearly always burdened). Max score = 88 | Baseline to visit 16 (14 weeks) |
| Actigraphy sleep assessment - Total sleep time | To assess standard sleep parameters using wearable devices (actigraph wristwatch): Total sleep time reported as time in minutes. | Screen to visit 16 (16 weeks) |
| Actigraphy sleep assessment - Wake after sleep onset | To assess standard sleep parameters using wearable devices (actigraph wristwatch): Wake after sleep onset (WASO) reported as time in minutes. | Screen to visit 16 (16 weeks) |
| Actigraphy sleep assessment - Sleep efficiency | To assess standard sleep parameters using wearable devices (actigraph wristwatch): Sleep efficiency reported as percentage. | Screen to visit 16 (16 weeks) |
| Physical activity | To assess daily activity using wearable devices: FitBit. | Screen to visit 16 (16 weeks) |
| D019636 |
| Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |
| D003072 | Cognition Disorders |