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Alzheimer DiseasePhase 1NCT03030105

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

A Phase 1 study testing BPN14770, Donepezil and Scopolamine 0.6 MG/ML in people with Alzheimer Disease, run by Tetra Discovery Partners at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Alzheimer Disease
What is being tested?
BPN14770, Donepezil and Scopolamine 0.6 MG/ML
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
38 participants
Where
1 siteUnited States
Study dates
Jan 2017to Jun 2017
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
  • Marked hypotension (systolic blood pressure [BP] ˂90 mmHg or diastolic BP ˂50 mmHg) or hypertension (systolic BP ˃150 mmHg or diastolic BP ˃100 mmHg) based on sitting values obtained. Out-of-range results may be repeated once at Screening. This exclusion applies to the vital signs performed at Screening and on Day -1 on Treatment Period 1.
  • Marked bradycardia (heart rate ˂45 beats per minute [bpm]) or tachycardia (heart rate ˃110 bpm) based on supine ECG values obtained. Out-of-range results may be repeated once at Screening. This exclusion applies to the vital signs performed at Screening and on Day -1 on Treatment Period 1.
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  • 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.
  • Donation of blood within the prior 4 weeks, or blood products within the prior 2 weeks, prior to first study drug administration.
  • Positive result for drugs of abuse, alcohol, or cotinine at Screening, or a positive drug or alcohol (breath) result upon admission to CRU.
  • History of clinically significant drug allergy that includes symptoms such as shortness of breath, rash, or edema. This includes known hypersensitivity to donepezil hydrochloride, scopolamine, or belladonna, alkaloids.
  • Inability or unwillingness to perform the Cogstate cognitive function tests.
  • A suicidal ideation intensity score of 2 or higher per screening Columbia Suicide Severity Rating Scale (C-SSRS) assessment and/or any suicidal behavior within the past 28 days.

Trial locations and contacts

1 site in 1 country.

United States1 site
  • ICON Early Phase Services, LLC

    Austin, Texas, 78209

Other trials in United States

About this study

Official title: A Randomized, Double-blind, Placebo-controlled, Single-dose, 6-Period Crossover Study to Evaluate the Effects of BPN14770 on Scopolamine-induced Cognitive Impairment in Healthy Volunteers

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.

Read the detailed description

A total of 38 subjects will be enrolled into the study. The study duration will be up to 12 weeks with 6 weeks of single-dose Treatment Visits. The study will consist of a Screening Visit (up to 28 days prior to first study drug administration), six inpatient Treatment Visits (Periods 1 through 6), and a Follow-Up/Early Termination Visit (7-10 days after the last dose of study medication). An additional study visit may be necessary to complete the required cognitive test familiarization if not completed during the Screening Visit. Each Treatment Visit will occur approximately one week apart, allowing a 6 to 8 day washout period.

Subjects will be randomized to 1 of 6 treatment sequences based on a computer-generated randomization schedule. Subjects will receive all 6 treatments as specified by the treatment sequence according to a 6 × 6 Williams Latin square design. The following treatments will be administered:

  1. Scopolamine placebo + BPN14770 placebo + donepezil placebo
  2. Scopolamine 0.5 mg + BPN14770 placebo + donepezil placebo
  3. Scopolamine 0.5 mg + BPN14770 10 mg + donepezil placebo
  4. Scopolamine 0.5 mg + BPN14770 50 mg + donepezil placebo
  5. Scopolamine 0.5 mg + donepezil 10 mg +BPN14770 placebo
  6. Scopolamine 0.5 mg + BPN14770 50 mg + donepezil 10 mg

During each of the Treatment Visits (Periods 1 through 6), subjects will be admitted to the Clinical Research Unit (CRU) the day prior to each study drug administration (Day -1) and discharged the day after study drug administration (Day 2). On the morning of study drug administration (Day 1), subjects will be given study drug (BPN14770, donepezil, or placebo) with 240mL of room temperature water 2 hours prior to the scopolamine or scopolamine placebo sc injection. The timing for study drug administration will be referred to as t-2 (Hour -2). Breakfast should be available approximately 30 minutes following the morning drug administration. Two hours after study drug administration, the scopolamine or scopolamine placebo sc injection will be administered. The time at which the scopolamine or scopolamine placebo sc injection is administered will be referred to as t0 (Hour 0).

Cognitive testing will be performed 30 minutes prior to treatment with scopolamine injection and at hours 1, 2, 3, 4, and 6 post-scopolamine injection.

PK samples will be collected during the treatment period to confirm study drug is present.

Safety assessments throughout the study will include physical exams, ECGs, vital signs, chemistry, hematology, and urinalysis.

Being tested
BPN14770, BPN14770 placebo, Donepezil, Donepezil placebo, Scopolamine 0.6 MG/ML
Keywords
Cognition, Dementia, Phosphodiesterase Type 4D, PDE4D, Scopolamine, Donepezil
Medical subject headings
Alzheimer Disease, Dementia

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • BPN14770Drug

    investigational drug

  • BPN14770 placeboDrug

    placebo

  • DonepezilDrug

    Also called Aricept

    comparator

  • Donepezil placeboDrug

    Also called Aricept placebo

    placebo

  • Scopolamine 0.6 MG/MLDrug

    Also called Hyoscine s.c.

    cognition impairment

  • Scopolamine placeboDrug

    Also called Hyoscine s.c. placebo

    placebo

Study groups in NCT03030105
Study groupRoleWhat they receive
A) P:P:PPlacebo comparatorScopolamine placebo : BPN14770 placebo : Donepezil placebo
Receives: Drug: BPN14770 placebo; Drug: Donepezil placebo; Drug: Scopolamine placebo
B) S:P:PPlacebo comparatorScopolamine 0.5mg : BPN14770 placebo : Donepezil placebo
Receives: Drug: BPN14770 placebo; Drug: Donepezil placebo; Drug: Scopolamine 0.6 MG/ML
C) S:B:PExperimentalScopolamine 0.5mg : BPN14770 10mg : Donepezil placebo
Receives: Drug: BPN14770; Drug: Donepezil placebo; Drug: Scopolamine 0.6 MG/ML
D) S:B:PExperimentalScopolamine 0.5mg : BPN14770 50mg : Donepezil placebo
Receives: Drug: BPN14770; Drug: Donepezil placebo; Drug: Scopolamine 0.6 MG/ML
E) S:P:DActive comparatorScopolamine 0.5mg : BPN14770 placebo : Donepezil 10mg
Receives: Drug: BPN14770 placebo; Drug: Donepezil; Drug: Scopolamine 0.6 MG/ML
F) S:B:DExperimentalScopolamine 0.5mg : BPN14770 50mg : Donepezil 10mg
Receives: Drug: BPN14770; Drug: Donepezil; Drug: Scopolamine 0.6 MG/ML

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Groton Maze Learning Test (GMLT)

    Measured: 2 hours post-scopolamine s.c. injection

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted24 Jan 2017 (estimated)
  2. Study startJan 2017
  3. Primary completionMay 2017
  4. Study completionJun 2017

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
Double blind
Who is masked
Participant, Investigator
Enrolment
38 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03030105
Sponsor's protocol ID
BPN14770-CNS-103
Status last verified
Oct 2018
First submitted
17 Jan 2017
Last updated
16 Oct 2018
Results posted
No
Data monitoring committee
No
Individual data sharing
No

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing BPN14770, Donepezil and Scopolamine 0.6 MG/ML in people with Alzheimer Disease, run by Tetra Discovery Partners at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 16 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Groton Maze Learning Test (GMLT) (time frame: 2 hours post-scopolamine s.c. injection). It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2018.

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