A Multiple Ascending Dose Study of BPN14770 in Healthy Young and Elderly Male or Female Subjects

NCT02840279 | Completed Phase 1

• 1 other identifier: BPN14770-CNS-102
• Study Type: interventional
• Target: 77
• Locations: 1 country
• Sites: 1

Brief Summary

This is a randomized, double-blind (Investigator and subject-blinded) placebo-controlled, multiple, ascending-dose study to evaluate the safety, tolerability, and pharmacokinetic profile of BPN14770 in healthy young and elderly male and female subjects and to provide a preliminary assessment of the cognitive effects of BPN14770 in healthy elderly subjects.

Conditions

Alzheimer's Disease

Keywords

cognition; dementia; phosphodiesterase type 4D; PDE4D

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events as a Measure of Safety and Tolerability

  Incidence and nature of adverse events (AEs) and serious adverse events (SAEs). Significant assessments reported as AEs or SAEs include clinical laboratory assessments and vital signs, physical and neurological examination, 12-lead electrocardiogram (ECG)

  2 weeks

Secondary Outcomes (2)

• Area Under the Curve from Time Zero to Twelve Hours [AUC0-12]

  2 weeks

• Area Under the Concentration Time Curve from Zero to 12 Hours, Corrected for Dose [AUC12/D]

  2 weeks

Other Outcomes (2)

• ISLT-D

  2 weeks

• GMLT-D

  2 weeks

Study Arms (2)

BPN14770

EXPERIMENTAL

An oral dose of BPN14770

Drug: BPN14770

Placebo

PLACEBO COMPARATOR

An oral dose of placebo matching BPN14770

Drug: Placebo

Interventions

BPN14770 DRUG

BPN14770 is an investigational new drug being developed for the treatment of Alzheimer's disease and other cognitive disorders. BPN14770 is a small molecule, subtype selective, negative allosteric modulator of phosphodiesterase 4D.

BPN14770

Placebo DRUG

Placebo

Eligibility Criteria

• Age: 25 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Healthy young males or females between the ages of 21 to 45, inclusive (Cohorts 1, 2, 3 and 7; female subjects must not be pregnant or breastfeeding), and healthy elderly males or females ≥ 65 years of age (Cohorts 4, 5, 6).
• Body mass index between 18 kg/m2 to 32 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 dosing), at least two years post-menopausal, or willing to use two barrier methods of contraception from initial screening until one month after taking the last dose of study drug. Barrier methods of contraception include diaphragm, cervical cap, male condom, female condom, and spermicidal foam and sponges. Menopausal status declared by females in the young cohorts will be verified by a follicle stimulating hormone (FSH) test at Screening. In addition, all females must have a negative pregnancy test within 48 hours before dosing on Day 1 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 dosing 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 entire duration of the confinement period, and return for outpatient visits.

You may not qualify if:

• Clinically significant abnormality, in the Investigator's judgement, indicated by the current hematology, biochemistry, or urinalysis tests, or from medical history, social history, vital signs, or physical examination.
• Positive serology results for hepatitis B surface antigen (HbsAg), hepatitis C virus (HCV), or human immunodeficiency virus (HIV).
• 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 supine and sitting values obtained at Screening, Day-1, or Day 1 predose. Out-of-range vital signs may be repeated once during each eligibility assessment (prior to the start of dosing on Day 1).
• Marked bradycardia (heart rate ˂45 beats per minute \[bpm\]) or tachycardia (heart rate ˃110 bpm) based on supine ECG values obtained at Screening, Day -1, or Day 1 predose. Out-of-range vital signs may be repeated once at each eligibility assessment (prior to the start of dosing on Day 1).
• History of hematological disorders (e.g., thrombocytopenia) in the immediate family (i.e., parents and siblings).
• 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 psychotropic drugs, sedative antihistamines, or other centrally active medications \[e.g., CNS beta blockers\], and moderate to strong inhibitors or inducers of CYP3A4, CYP2D6, or other cytochromes). 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 test medication or the cognitive testing.
• Any history of alcohol or drug abuse 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 within 24 hours of admission into the study on Day -2.
• Active smokers or tobacco users (e.g., chew and snuff) who are unable to discontinue tobacco use at least 3 months prior to admission to the study on Day -2 and refrain from using tobacco during the study treatment and evaluation period.
• 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 or blood products (including plasma) during the 8 weeks before the first administration of study drug on Day 1.
• Positive screen for drugs of abuse or cotinine (at screen or upon admission), or a positive alcohol result (upon admission).

Sponsors & Collaborators

• Tetra Discovery Partners: lead

Study Sites (1)

Jasper Clinic

Kalamazoo, Michigan, 49007, United States

Location

Related Publications (1)

• Cowie JM, Gurney ME. The Use of Facebook Advertising to Recruit Healthy Elderly People for a Clinical Trial: Baseline Metrics. JMIR Res Protoc. 2018 Jan 24;7(1):e20. doi: 10.2196/resprot.7918.

  PMID: 29367186 DERIVED

MeSH Terms

Conditions

Alzheimer Disease; Dementia

Interventions

BPN14770

Condition Hierarchy (Ancestors)

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

Study Officials

• Scott Reines, MD, PhD

  Tetra Discovery Partners

  STUDY CHAIR

Study Design

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

Study Record Dates

• First Submitted: July 19, 2016
• First Posted: July 21, 2016
• Study Start: June 1, 2016
• Primary Completion: November 1, 2016
• Study Completion: December 1, 2016
• Last Updated: January 18, 2017

Record last verified: 2016-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)