Bioavailability, Safety, and Tolerability of BIS-001 ER

Evaluation of the Bioavailability, Safety, and Tolerability of BIS-001 ER Following Multiple Dose Administration in Healthy Subjects

This study investigates the safety, tolerability, and pharmacokinetics of BIS-001 ER in healthy volunteers. Subjects will be dosed twice daily, with a dose escalation occurring every 2-3 days until a maximum dose of 5mg per day is reached.

Study Overview

• Status: Completed
• Conditions: Epilepsy, Complex Partial
• Intervention / Treatment: Drug: BIS-001 ER

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Phase 1

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Parkville, Victoria, Australia, 3050
      • The Royal Melbourne Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Speak English with sufficient proficiency to read and comprehend the Informed Consent document, and to communicate with study staff.
2. Be able to consent to participate by signing the Informed Consent document after a full explanation of the nature and purpose of this study.
3. Have signed the Informed Consent before any study-specific procedures are performed
4. Be males or females between 18 - 45 years of age.
5. Have a negative urinary pregnancy test upon admission to the site on Day 1
6. Be in good general health in the judgment of the Principal Investigator based upon medical history, physical examination, standard 12-lead electrocardiogram (ECG), and clinical laboratory evaluations obtained within the two weeks prior to enrollment.
7. Be able to comply with all study-specified procedures.
8. Weight between 40 and 100 kg

Exclusion Criteria:

1. Has taken Huperzine A.
2. Is planning to become pregnant or impregnate spouse, not using an acceptable method of birth control (defined as use of double-barrier birth control methods, use of oral contraceptives, or surgical sterilization), pregnant or nursing
3. Has a pre-existing medical condition (including an existing progressive or degenerative neurological disorder) or takes medications that, in the Principal Investigator's opinion, could interfere with the subject's suitability for participation in the study.
4. Has a history or evidence of significant psychiatric disturbance or illness, including alcohol or drug abuse within the past 2 years, or symptoms of psychosis (hallucinations, delusions) in the last 5 years.
5. Has had any clinical laboratory abnormalities within the past two months, prior to screening, considered of clinical significance by the Principal Investigator
6. Is on concomitant therapy with non-anti-epileptic drugs (AEDs) that are cholinergic.
7. Has participated in any clinical investigational drug or device study within four weeks prior to study entry.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: BIS-001 ER; The subjects will be dosed twice daily (BID); in an on-site setting at dose initiation and at times of dose escalation to evaluate safety, and for specimen collection for routine laboratory and pharmacokinetic analysis. Subjects will be discharged and compliance of BID dosing will be monitored via twice daily phone calls by site staff. The initial dose will be 0.5mg BID with a dose escalation every 2-3 days until a maximum tolerated dose is observed or a maximum of 2.5mg BID dose is obtained.

Drug: BIS-001 ER; BIS-001 ER is an extended release formulation of the nutritional supplement Huperzine A.; Other Names: Huperzine A

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Maximum serum concentration; Cmax	Bioavailability/Pharmacokinetic Assessments	16 Weeks
Area under the curve; AUC	Bioavailability/Pharmacokinetic Assessments	16 Weeks
Time of maximum serum concentration; Tmax	Bioavailability/Pharmacokinetic Assessments	16 Weeks
Half-life; t1/2	Bioavailability/Pharmacokinetic Assessments	16 Weeks
Terminal elimination	Bioavailability/Pharmacokinetic Assessments	16 Weeks
Clearance	Bioavailability/Pharmacokinetic Assessments	16 Weeks
Volume of distribution	Bioavailability/Pharmacokinetic Assessments	16 Weeks
Mean residence time	Bioavailability/Pharmacokinetic Assessments	16 Weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Tolerability Assessments - Adverse Events	Adverse events will be defined, documented, evaluated (mild/moderate/severe/life threatening; serious/non-serious; expected/unexpected; causally related to study drug or not) and reported according to all applicable institutional and governmental requirements and guidance.	16 Weeks
Safety and Tolerability Assessments - Vital Signs	Vital signs (e.g. blood pressure) will be monitored through the first 8 hrs after drug administration, as well as at Baseline and pre-dose.	16 Weeks
Safety and Tolerability Assessments - Neurological Evaluation	A standard neurological examination will be performed according to the study-specific timeline. Clinically significant new or worsened abnormalities as compared to baseline findings will have to be reported as AEs.	16 Weeks
Safety and Tolerability Assessments - Physical Evaluation	A standard physical examination will be performed according to the study-specific timeline. Clinically significant new or worsened abnormalities as compared to baseline findings will have to be reported as AEs.	16 Weeks
Safety and Tolerability Assessments - ECG Evaluation	A standard 12-lead ECG in a supine position after a 5-minute rest will be performed according to the study-specific timeline. The Investigator will determine whether the results of the ECG are normal or abnormal and assess the clinical significance of any abnormality. ECG tracings will be reviewed by a cardiologist if required.	16 Weeks
Safety and Tolerability Assessments - Clinical Laboratory Studies: Hematology	Laboratory assessments will be conducted using standard methods.	16 Weeks
Safety and Tolerability Assessments - Clinical Laboratory Studies: Biochemistry	Laboratory assessments will be conducted using standard methods.	16 Weeks
Safety and Tolerability Assessments - Clinical Laboratory Studies: Urinalysis	Laboratory assessments will be conducted using standard methods.	16 Weeks

Collaborators and Investigators

• Sponsor: Supernus Pharmaceuticals, Inc.
• Collaborators: Melbourne Health
• Investigators: Study Chair: Stephen D Collins, President and CEO

Study record dates

Study Major Dates

• Study Start (Actual): May 22, 2017
• Primary Completion (Actual): September 30, 2017
• Study Completion (Actual): September 30, 2017

Study Registration Dates

• First Submitted: May 15, 2017
• First Submitted That Met QC Criteria: May 15, 2017
• First Posted (Actual): May 17, 2017

Study Record Updates

• Last Update Posted (Actual): January 18, 2018
• Last Update Submitted That Met QC Criteria: January 16, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Epilepsy; Epilepsies, Partial; Epilepsy, Complex Partial; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Cholinergic Agents; Enzyme Inhibitors; Neuroprotective Agents; Protective Agents; Cholinesterase Inhibitors; Huperzine A
• Other Study ID Numbers: BNI-01-1b

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No