Open-label, Normal Healthy Volunteer Clinical Trial of a Novel Ondansetron Formulation

Phase Ia/Ib Study of Normal Healthy Volunteer Clinical Trial of a Novel Ondansetron Formulation

The goals of this open-label Phase Ia study are to evaluate the Pharmacokinetics (PK) profiles of new novel single-dose Ondansetron Pulsatile Release (Ond-PR) formulations in normal healthy volunteers. After this initial phase, the investigators will follow with the Phase Ib study to determine Pharmacokinetic/Pharmacodynamic (PK/PD), safety, and tolerability interactions following simultaneous administration of these ondansetron formulations with a 10 mg Methylphenidate Immediate Release (MPh-IR) tablet in normal healthy volunteers.

We will compare 2 different pulsatile-release formulations of ondansetron, PR1 and PR2. Ond-PR1 is a pH-sensitive formulation while Ond-PR2 is osmotic-sensitive.

Inclusion Criteria:

• Subjects must give written informed consent to participate in the study prior to screening. Consent will be documented by the subject's dated signature that will be counter-signed and dated by a witness.
• Healthy non-smoking, by history, adult male and/or female volunteers between the ages of 18 and 45 years old and with a Body Mass Index (BMI) of ≥18-≤32 kg/m2.
• Subjects must be in good health as determined by screening medical history, physical examination, vital signs, electrocardiogram, blood chemistry, hematology, and urinalysis (U/A) performed at screening.
• Normal Hematology Clinical Laboratory, Results, including: Normal White Blood Cell (WBC) and differential, Hematocrit, Hemoglobin, Platelet Counts
• Normal Electrocardiogram (ECG) and a measure between Q wave and T wave in the heart's electrical cycle at baseline (QTcB) ≤ 430 msec (males) or ≤ 430 msec (females)

Exclusion Criteria:

• Male and/or female subjects who consume more than 28 units of alcohol per week (one unit of alcohol equals ½ pint of beer, 4 ounces of wine, or 1 ounce of spirits) or those subjects who have a significant history of alcoholism or drug/chemical abuse within the last 2 years. Subjects must agree to abstain from alcohol, cola, tea, coffee, chocolate and other caffeinated drink and food from 2 days before Period 1, Day 1 and throughout confinement.
• Subjects who have used tobacco products or nicotine-containing products (including smoking cessation aids, such as gums or patches) within 3 months prior to Day -1.
• Subjects with positive results on tests for drugs of abuse, or alcohol at screening and check-in.
• Concomitant Medications: Any drugs, vitamins, over the counter (OTC) medicines and nutraceuticals if used within the previous 7 days of check-in as deemed clinically significant by the Principal Investigator (PI).
• Subjects who have used any drugs or substances known to be strong inhibitors or strong inducers of CYP 3A4/5 enzymes (also known as cytochrome P-450 enzymes) or P-Glycoprotein (Pgp) within 30 days prior to Period 1, Day -1. Subjects must agree to abstain from grapefruit/grapefruit juice and seville oranges for 2 days before period Ia, Day -1 and throughout the study.
• Use of other investigational drugs at the time of enrollment (consenting), or 5 half-lives of enrollment whichever is longer; or longer if required by local regulations, and for any other limitation of participation in an investigational trial based on local regulations.
• History of unstable psychiatric illness requiring medications or hospitalization within the previous 12 months.
• History of concurrent illness that required hospitalization within 14 days prior to Day 1 of the study.
• Any condition that in the clinical judgment of the Investigator would make the subject unsuitable for participation.
• Allergies or allergic reactions to any of the products used in this study.
• Subjects who have had a clinically significant illness within 4 weeks prior to Day -1.
• Subjects with QTcB interval duration >430 msec (males) or >450 (females) obtained from the ECG recorder's measurements on the screening ECG taken after at least 5 minutes of quiet rest in supine position.
• History or current evidence of clinically significant hepatic, renal, cardiovascular (i.e., deep venous thrombosis, pulmonary embolism), psychological, pulmonary, metabolic, endocrine, neurologic (i.e., transient ischemic attack or stroke within the past 6 months) infectious, gastrointestinal (i.e., any condition which may affect drug absorption) hematologic, oncologic disease, retinopathy, or other medical disorders, as determined by screening history, physical examination, laboratory test results, or 12-lead ECG.
• History of unexplained syncope.
• Subjects with creatinine clearance < 80 mL/min (based on Cockcroft-Gault equation).
• Subjects who, in the opinion of the Investigator, should not participate in the study.
• Any employee of the Duke Clinical Research Unit (DCRU).
• Subjects who have blood relatives of another study participant.
• Subjects must be compliant and meet all inclusion and exclusion criteria unless, following discussions between the Principal Investigator or his designate, it is determined that a minor exception is not indicative of clinically significant safety risk and unlikely to confound the results of the study.