NCT02221622

Brief Summary

The purpose of this study is to evaluate the safety and tolerability of allopregnanolone, a naturally occurring brain steroid, in mild cognitive impairment and early Alzheimer's disease participants. The primary goal is to determine the maximally tolerated dose.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
24

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Aug 2014

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

July 2, 2014

Completed
1 month until next milestone

Study Start

First participant enrolled

August 1, 2014

Completed
19 days until next milestone

First Posted

Study publicly available on registry

August 20, 2014

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

February 1, 2018

Completed
Last Updated

July 5, 2019

Status Verified

May 1, 2018

Enrollment Period

3.5 years

First QC Date

July 2, 2014

Last Update Submit

July 2, 2019

Conditions

Mild Cognitive ImpairmentAlzheimer Disease

Keywords

Alzheimer's diseaseMild Cognitive ImpairmentDementiaRegenerative therapeutic

Outcome Measures

Primary Outcomes (5)

  • Safety profile: Adverse events

    Incidence and severity of treatment emergent adverse events assessed weekly per treatment arm.

    From Baseline to week 16

  • Safety profile: Clinical laboratory measurements

    Evaluating the proportion of subjects exceeding pre-established critical values per treatment arm: Alanine aminotransferase (ALT, U/L) \> 5 times upper normal limit Aspartate aminotransferase (AST, U/L) \> 5 times upper normal limit Total serum bilirubin (mg/dl) \> 2 times upper normal limit Serum creatinine (mg/dl) \> 2 times upper normal limit Serum creatine phosphokinase (U/L) \> 5 times upper normal limit

    From Baseline to week 13

  • Safety profile: ARIA

    MRI based assessment of amyloid related imaging abnormalities (ARIA); proportion of subjects with ARIA

    From Baseline to week 13

  • Safety profile: Physical and neurological examination

    To evaluate the proportion of abnormal examination findings of subjects in each treatment arm.

    From Baseline to week 16

  • Tolerability - Maximum tolerated dose (MTD)

    Onset of sedation will define the upper most limit of drug dose

    From Baseline to week 12

Secondary Outcomes (7)

  • Pharmacokinetic profile after single and multiple doses: Maximum Concentration (Cmax)

    Weeks: 1 and 12

  • Pharmacokinetic profile after single and multiple doses: time attain to Cmax (Tmax)

    Weeks: 1 and 12

  • Pharmacokinetic profile after single and multiple doses: Area under the curve (AUC)

    Weeks: 1 and 12

  • Pharmacokinetic profile after single and multiple doses: Drug Clearance (CL)

    Weeks: 1 and 12

  • Pharmacokinetic profile after single and multiple doses: apparent volume of distribution at steady state (Vss)

    Weeks: 1 and 12

  • +2 more secondary outcomes

Study Arms (4)

Allopregnanolone 2 mg

EXPERIMENTAL

Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks

Drug: Allopregnanolone injection (intravenous solution)

Allopregnanolone 4 mg

EXPERIMENTAL

Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks

Drug: Allopregnanolone injection (intravenous solution)

Allopregnanolone 6-18 mg

EXPERIMENTAL

Drug: Allopregnanolone injection (intravenous solution) once per week for 12 weeks

Drug: Allopregnanolone injection (intravenous solution)

Placebo

PLACEBO COMPARATOR

Drug: Placebo injection (intravenous solution) once per week for 12 weeks

Drug: Placebo injection (intravenous solution)

Interventions

Allopregnanolone injection (intravenous solution)DRUG

Allopregnanolone intravenous infusion

Also known as: 3α,5α-tetrahydroprogesterone, 3α-hydroxy-5α-pregnan-20-one
Allopregnanolone 2 mgAllopregnanolone 4 mgAllopregnanolone 6-18 mg
Placebo injection (intravenous solution)DRUG

Placebo intravenous infusion

Placebo

Eligibility Criteria

Age55 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Men or postmenopausal women
  • years of age or older
  • Diagnosis of MCI due to AD or mild AD
  • MMSE \> 20 at screen
  • Capacity to provide informed consent
  • Residing in the community with a caregiver able to accompany the patient to clinic visits
  • No medical contraindications to participation
  • Willingness to comply with study procedures

You may not qualify if:

  • 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
  • MRI indicative of any other significant abnormality, including but not limited to evidence of a cerebral contusion, encephalomalacia, aneurysms, vascular malformations, subdural hematoma, or space occupying lesions
  • Any condition that would contraindicate an MRI such as the presence of metallic objects in the eyes, skin, heart, or body

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Southern California - Alzheimer Disease Research Center - Healthcare Consultation Center II

Los Angeles, California, 90033, United States

Location

Related Publications (1)

  • Hernandez GD, Solinsky CM, Mack WJ, Kono N, Rodgers KE, Wu CY, Mollo AR, Lopez CM, Pawluczyk S, Bauer G, Matthews D, Shi Y, Law M, Rogawski MA, Schneider LS, Brinton RD. Safety, tolerability, and pharmacokinetics of allopregnanolone as a regenerative therapeutic for Alzheimer's disease: A single and multiple ascending dose phase 1b/2a clinical trial. Alzheimers Dement (N Y). 2020 Dec 16;6(1):e12107. doi: 10.1002/trc2.12107. eCollection 2020.

    PMID: 33344752DERIVED

MeSH Terms

Conditions

Cognitive DysfunctionAlzheimer DiseaseDementia

Interventions

Pregnanolone

Condition Hierarchy (Ancestors)

Cognition DisordersNeurocognitive DisordersMental DisordersBrain DiseasesCentral Nervous System DiseasesNervous System DiseasesTauopathiesNeurodegenerative Diseases

Intervention Hierarchy (Ancestors)

PregnanesSteroidsFused-Ring CompoundsPolycyclic Compounds

Study Officials

  • Roberta D Brinton, Ph.D.

    University of Southern California

    PRINCIPAL INVESTIGATOR

  • Lon S Schneider, M.D.

    University of Southern California

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 2, 2014

First Posted

August 20, 2014

Study Start

August 1, 2014

Primary Completion

February 1, 2018

Study Completion

February 1, 2018

Last Updated

July 5, 2019

Record last verified: 2018-05

Locations

US(1)