Alzheimer Dementia
Conditions
Keywords
Alzheimer's disease, Mild cognitive impairment, Dementia, Regenerative therapeutic, Drug development
Brief summary
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.
Detailed description
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).
Interventions
DRUGAllopregnanolone
Administration of weekly IM injections of Allopregnanolone.
Sponsors
University of Arizona
University of Southern California
Alzheimer's Association
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Single-arm, open-label study
Eligibility
Sex/Gender
ALL
Age
55 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Provision of signed and dated informed consent form * Stated willingness to comply with all study procedures and availability for the duration of the study * Men or postmenopausal women, aged 55 years or older * Diagnosis of MCI due to AD or mild AD * In good general health as evidenced by medical history and with no medical contraindications to participation * MMSE \> 20 at screen * Caregiver willing and capable to accompany the patient to clinic visits
Exclusion criteria
* Daily use of benzodiazepines, sedative/hypnotics, anticonvulsants, antipsychotics, and other drugs that might interact with the GABA-A receptor complex. * Seizure disorder, history of stroke, focal brain lesion, traumatic brain injury, substance abuse, malignancy. * Clinically significant laboratory or ECG abnormality obtained at screening visit. * MRI indicative of significant abnormality, including but not limited to evidence of a single prior hemorrhage or infarct \>1 cm3, multiple lacunar infarcts (\>1) or evidence of a single prior infarct \>1cm3, evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions (e.g. abscess or tumor). * Has any contraindications for MRI studies, including claustrophobia, the presence of metal (ferromagnetic) implants, or a cardiac pacemaker that is not compatible with MRI. * Is currently enrolled in a clinical trial involving an off-label use of an investigational drug or device, or concurrently enrolled in any other type of medical research or observational study judged not to be scientifically or medically compatible with this study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety - Adverse events | From baseline to visit 16 (14 weeks) | Incidence and severity of treatment emergent adverse events assessed weekly. |
| Safety - clinical laboratory measures | From Baseline to visit 16 (14 weeks) | Proportion of subjects exceeding pre-established critical laboratory values. |
| Safety - clinical assessment | From Baseline to visit 16 (14 weeks) | Proportion of subjects with abnormal findings in physical/neurological exams, vital signs and electrocardiograms. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Pharmacokinetic parameter - Cmax | Visits 3 - 6 (up to 4 weeks) | Determine maximum serum concentration of Allo after IM administration of each dose. |
| Pharmacokinetic parameter - AUC | Visits 3 - 6 (up to 4 weeks) | Determine the area under the curve after each IM administration of Allo. |
| Pharmacokinetic parameter - Tmax | Visits 3 - 6 (up to 4 weeks) | Determine the time at which Cmax is attained. |
| Pharmacokinetic parameter - Clearance | Visits 3 - 6 (up to 4 weeks) | Pharmacokinetic measurement of the volume of plasma from which Allo is completely removed per unit time. |
| Pharmacokinetic parameter - Volume of distribution | Visits 3 - 6 (up to 4 weeks) | Determine the volume of distribution at steady state of Allo. |
| Satisfaction and feasibility of home nurse survey | Visits 8-9 and 11-15 (up to 8 weeks) | 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). |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORRoberta D Brinton, PhD
University of Arizona
PRINCIPAL_INVESTIGATORLon S Schneider, MD, MS
University of Southern California
Outcome results
None listed