Study to Evaluate the Effects of BPN14770 on Scopolamine-induced Cognitive Impairment in Healthy Volunteers

NCT03030105 | Completed Phase 1

• 1 other identifier: BPN14770-CNS-103
• Study Type: interventional
• Target: 38
• Locations: 1 country
• Sites: 1

Brief Summary

This is a Phase 1, randomized, double-blind, placebo-controlled, 6-period crossover study to evaluate the effects of BPN14770 10 mg and 50 mg in reversing scopolamine-induced cognitive impairment in healthy volunteers. A positive control, donepezil 10 mg, will be included, and additivity of BPN14770 50 mg to donepezil 10 mg in reversing scopolamine effects will also be evaluated.

Conditions

Alzheimer Disease

Keywords

Cognition; Dementia; Phosphodiesterase Type 4D; PDE4D; Scopolamine; Donepezil

Outcome Measures

Primary Outcomes (1)

• Groton Maze Learning Test (GMLT)

  2 hours post-scopolamine s.c. injection

Other Outcomes (6)

• Detection Test (DET)

  30 minutes prior and at 1, 2, 3, 4, and 6 hours post-scopolamine sc injection

• One Card Learning Test (OCL)

  30 minutes prior and at 1, 2, 3, 4, and 6 hours post-scopolamine sc injection

• One Back Test (ONB)

  30 minutes prior and at 1, 2, 3, 4, and 6 hours post-scopolamine sc injection

Study Arms (6)

A) P:P:P

PLACEBO COMPARATOR

Scopolamine placebo : BPN14770 placebo : Donepezil placebo

Drug: BPN14770 placebo; Drug: Donepezil placebo; Drug: Scopolamine placebo

B) S:P:P

PLACEBO COMPARATOR

Scopolamine 0.5mg : BPN14770 placebo : Donepezil placebo

Drug: BPN14770 placebo; Drug: Donepezil placebo; Drug: Scopolamine 0.6 MG/ML

C) S:B:P

EXPERIMENTAL

Scopolamine 0.5mg : BPN14770 10mg : Donepezil placebo

Drug: BPN14770; Drug: Donepezil placebo; Drug: Scopolamine 0.6 MG/ML

D) S:B:P

EXPERIMENTAL

Scopolamine 0.5mg : BPN14770 50mg : Donepezil placebo

Drug: BPN14770; Drug: Donepezil placebo; Drug: Scopolamine 0.6 MG/ML

E) S:P:D

ACTIVE COMPARATOR

Scopolamine 0.5mg : BPN14770 placebo : Donepezil 10mg

Drug: BPN14770 placebo; Drug: Donepezil; Drug: Scopolamine 0.6 MG/ML

F) S:B:D

EXPERIMENTAL

Scopolamine 0.5mg : BPN14770 50mg : Donepezil 10mg

Drug: BPN14770; Drug: Donepezil; Drug: Scopolamine 0.6 MG/ML

Interventions

BPN14770 DRUG

investigational drug

C) S:B:P; D) S:B:P; F) S:B:D

BPN14770 placebo DRUG

placebo

A) P:P:P; B) S:P:P; E) S:P:D

Donepezil DRUG

comparator

Also known as: Aricept

E) S:P:D; F) S:B:D

Donepezil placebo DRUG

placebo

Also known as: Aricept placebo

A) P:P:P; B) S:P:P; C) S:B:P; D) S:B:P

Scopolamine 0.6 MG/ML DRUG

cognition impairment

Also known as: Hyoscine s.c.

B) S:P:P; C) S:B:P; D) S:B:P; E) S:P:D; F) S:B:D

Scopolamine placebo DRUG

placebo

Also known as: Hyoscine s.c. placebo

A) P:P:P

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy males or females between the ages of 18 to 55 years at Screening.
• Body mass index between 18 kg/m2 to 33 kg/m2, inclusive, and body weight of \>50 kg (110 pounds).
• Female subjects must be surgically sterile (bilateral tubal ligation, hysterectomy, or bilateral oophorectomy at least 6 months prior to first study drug administration), at least two years post-menopausal, or willing to either (1) utilize hormonal contraception plus use one barrier method or (2) use two barrier methods of contraception from initial screening until one month after taking the final dose. Barrier methods of contraception include diaphragm, cervical cap, male condom, female condom, and spermicidal foam and sponges. An intrauterine device (IUD) is also considered a barrier method of contraception in this study; if the subject is using an IUD, she will need to use an additional barrier method of contraception. Menopausal status will be verified by testing for follicle stimulating hormone (FSH ≥25 mIU/mL) at Screening. In addition, all females must have a negative blood test for pregnancy within 28 days during the Screening period and negative urine test for pregnancy on Day-1 of each Treatment Visit regardless of childbearing potential.
• Male subjects must be willing to inform female partners of their participation in the study and must agree to use adequate contraceptive methods (vasectomy performed at least 6 months prior to first study drug administration, or use at least one barrier method of birth control).
• Able to understand the study procedures, voluntarily consent to participate in this study, and provide written informed consent prior to start of any study-specific procedures.
• Willing and able to remain in the study unit for the required periods and return for each treatment of the six treatment periods, including the outpatient visits.

You may not qualify if:

• Clinically significant abnormality, in the Investigator's judgement, in Screening hematology, chemistry, or urinalysis tests, or from medical history, social history, vital sign, or physical examination
• Active liver disease or positive serology results for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• Abnormal liver function test at the Screening Visit (aspartate aminotransferase or alanine aminotransferase \>2 × the upper limit of normal \[ULN\]; total bilirubin \>1.5 × ULN; or alkaline phosphatase \>2 × ULN based on appropriate age and gender normal values).
• Current or past history of angle closure glaucoma, or diagnosis of angle closure glaucoma.
• Current or past history of significant (in the Investigator's judgement) cardiovascular, cerebrovascular, pulmonary, renal, or liver disease. Stable, well-controlled hypertension and hyperlipidemias are allowed.
• Clinically important or significant conduction abnormalities on single ECG or evidence or history of long QT syndrome based on supine ECG values obtained at Screening. Out-of-range results may be repeated once at Screening.
• Current or past history of gastric or duodenal ulcers or other diseases of the gastrointestinal tract that could interfere with absorption of study drug. Note: Subjects with a history of appendectomy or cholecystectomy may be enrolled.
• Active acute or chronic infectious diseases.
• Unable to discontinue medications including anticholinergic agents, psychotropic drugs, sedative antihistamines, or other centrally active medications \[e.g., CNS- penetrant beta blockers\], and moderate to strong inhibitors or inducers of CYP3A4, CYP2D6, or other cytochromes) 14 days prior to the first dose of study drug (Period 1, Day 1) and during the study (Follow-Up). Other prescription or non-prescription drugs such as antihypertensive or cholesterol lowering drugs are allowed, if, in the Investigator's judgement, they would not interfere with the study medication or the cognitive testing.
• Unable to discontinue and abstain from over-the-counter, herbal preparations, dietary supplements, nutraceuticals, vitamins and minerals at least 7 days prior to the first dose of study drug and during the study. The one exception to this rule is acetaminophen, which may be taken for minor ailments at doses up to 1000 mg per day.
• Any history of alcohol or other substance abuse, including marijuana, within the previous year prior to the Screening visit (per the current edition of the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition: DSM-5), or regular (daily) consumption of alcohol exceeding two bottles of beer, or the equivalent amount of other forms of alcohol (1 serving = 12 oz beer, 5.0 oz wine, or 1.5 oz distilled spirits).
• Any use of alcohol, grapefruit, marijuana, or other psychotropic agent within 12 hours of admission into the CRU.
• Active smokers or tobacco users (e.g., chew and snuff) who are unable to discontinue tobacco use or nicotine-containing products (including e-cigarettes) at least 4 weeks prior to Screening and to refrain from using during the study.
• Inability or unwillingness to comply with the protocol or likely inability to complete the study.
• Participation in other clinical studies involving investigational drug within the previous 30 days prior to the Screening Visit.

Sponsors & Collaborators

• Tetra Discovery Partners: lead

Study Sites (1)

ICON Early Phase Services, LLC

Austin, Texas, 78209, United States

Location

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

BPN14770; Donepezil; Scopolamine

Condition Hierarchy (Ancestors)

Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Tauopathies; Neurodegenerative Diseases; Neurocognitive Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indans; Indenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Polycyclic Compounds; Scopolamine Derivatives; Tropanes; Azabicyclo Compounds; Aza Compounds; Belladonna Alkaloids; Solanaceous Alkaloids; Alkaloids; Bridged Bicyclo Compounds, Heterocyclic; Heterocyclic Compounds, Bridged-Ring

Study Officials

• Cassandra Key, MD

  ICON Early Phase Services, LLC

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 17, 2017
• First Posted: January 24, 2017
• Study Start: January 1, 2017
• Primary Completion: May 1, 2017
• Study Completion: June 1, 2017
• Last Updated: October 16, 2018

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)