A Randomized, Double-blind, Placebo-controlled, Multiple Ascending Dose Study to Examine the Safety, Tolerability, Pharmacokinetic, and Preliminary Cognitive Profile of BPN14770 in Healthy Young and Elderly Male and Female Subjects

Tetra Discovery Partners1 site in 1 country77 target enrollmentJune 2016

ConditionsAlzheimer's Disease

InterventionsBPN14770 Placebo

DrugsBPN14770 Placebo

Overview

Phase: Phase 1
Intervention: BPN14770
Conditions: Alzheimer's Disease
Sponsor: Tetra Discovery Partners
Enrollment: 77
Locations: 1
Primary Endpoint: Number of Participants with Adverse Events as a Measure of Safety and Tolerability
Status: Completed
Last Updated: 9 years ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials

Overview

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.

Detailed Description

Objectives: 1. To evaluate the safety and tolerability profile of multiple oral ascending dose levels of BPN14770 in healthy young and elderly subjects. 2. To characterize the plasma pharmacokinetic profile of BPN14770 following oral administration in healthy young and elderly subjects. 3. To provide preliminary assessment of the cognitive effect of BPN14770 in healthy elderly subjects.

Registry

clinicaltrials.gov

Start Date

June 2016

End Date

December 2016

Last Updated

9 years ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Tetra Discovery Partners

Responsible Party

Sponsor

Eligibility Criteria

Inclusion Criteria

•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.

Exclusion Criteria

•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).
•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 (see Exclusion #10).
•History of hematological disorders (e.g., thrombocytopenia) in the immediate family (i.e., parents and siblings).
•Clinically important or significant conduction abnormalities on single ECG (including QTc interval ˃450 msec) or evidence or history of long QT syndrome. This exclusion applies to the ECGs obtained at Screening, Day -1, and Day 1 predose.
•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.

Arms & Interventions

BPN14770

An oral dose of BPN14770

Intervention: BPN14770

Placebo

An oral dose of placebo matching BPN14770

Intervention: Placebo

Outcomes

Primary Outcomes

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

Time Frame: 2 weeks

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)

Secondary Outcomes

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)