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

NCT01290276 | Completed Phase 1

• 4 other identifiers: Pro00024378110034 (Pro00024378)110195 (Pro00026674)Pro00026674
• Study Type: interventional
• Target: 6
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Healthy

Keywords

Ondansetron; Methylphenidate

Outcome Measures

Primary Outcomes (1)

• The release profile of Ondansetron Pulsatile Release (Ond-PR) in the human gastrointestinal (GI) tract matches the one predicted from test tube dissolution experiments.

  Serum levels of ondansetron after oral administration of Ond-PR in healthy human volunteers. Standard PK parameters will be calculated based on the serum levels to verify that the drug levels reach the peak blood concentration 5 - 6 hours after oral administration. Time Frame: Blood samples will be taken immediately before oral Ond-PR administration, followed by sampling at 0.5, 1, 2, 2.5, 3, 3.5, 4, 4.5, 5, 6 and 10 hours after drug administration.

  The time to reach peak blood concentration (tmax) for oral Ondansetron Standard (Ond-St) is ~2 hours (h). Therefore, tmax for Ond-PR with in vitro dissolution time of 3 - 4 h is expected to be 5 - 6 h (i.e., 3 - 4 h delay + normal absorption time).

Secondary Outcomes (1)

• To determine drug-drug interactions of Ond-PR with a simultaneously-administered MPh-IR.

  5 - 6 h

Study Arms (2)

Ond-PR1 followed by (Ond-PR1 + MPh-IR)

EXPERIMENTAL

Oral dose of 8 mg of ondansetron pulsatile-release formulation 1 followed by Oral dose of 8 mg of ondansetron pulsatile-release formulation 1 (Ond-PR1) plus 10 mg methylphenidate immediate release (Mph-IR)

Drug: Ond-PR1; Drug: Ond-PR1 + MPh-IR; Drug: Ond-PR2; Drug: Ond-PR2 +_ MPh-IR

Ond-PR2 followed by (Ond-PR2 + MPh-IR)

EXPERIMENTAL

Oral dose of 8 mg of ondansetron pulsatile-release formulation 2 followed by Oral dose of 8 mg of ondansetron pulsatile-release formulation 2 (Ond-PR2) plus 10 mg methylphenidate immediate release (Mph-IR)

Drug: Ond-PR1; Drug: Ond-PR1 + MPh-IR; Drug: Ond-PR2; Drug: Ond-PR2 +_ MPh-IR

Interventions

Ond-PR1 DRUG

Single oral dose of 8 mg of ondansetron pulsatile-release formulation 1 (Ond-PR1)

Also known as: Zofran (ondansetron hydrochloride)

Ond-PR1 followed by (Ond-PR1 + MPh-IR); Ond-PR2 followed by (Ond-PR2 + MPh-IR)

Ond-PR1 + MPh-IR DRUG

Single oral dose of 8 mg of ondansetron pulsatile-release formulation 1 (Ond-PR1) plus 10 mg methylphenidate immediate release (Mph-IR)

Also known as: Zofran (ondansetron hydrochloride), Ritalin (methylphenidate hydrochloride)

Ond-PR1 followed by (Ond-PR1 + MPh-IR); Ond-PR2 followed by (Ond-PR2 + MPh-IR)

Ond-PR2 DRUG

Single oral dose of 8 mg ondansetron pulsatile-release formulation 2 (Ond-PR2)

Also known as: Zofran (ondansetron hydrochloride)

Ond-PR1 followed by (Ond-PR1 + MPh-IR); Ond-PR2 followed by (Ond-PR2 + MPh-IR)

Ond-PR2 +_ MPh-IR DRUG

Single oral dose of 8 mg of ondansetron pulsatile-release formulation 2 (Ond-PR2) plus 10 mg methylphenidate immediate release (Mph-IR)

Also known as: Zofran (ondansetron hydrochloride), Ritalin (methylphenidate hydrochloride)

Ond-PR1 followed by (Ond-PR1 + MPh-IR); Ond-PR2 followed by (Ond-PR2 + MPh-IR)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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)

You may not qualify if:

• 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).

Sponsors & Collaborators

• Tong Lee: lead

Study Sites (1)

Duke University Medical Center

Durham, North Carolina, 27710, United States

Location

MeSH Terms

Interventions

Ondansetron; Methylphenidate

Intervention Hierarchy (Ancestors)

Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Carbazoles; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds, 3-Ring; Phenylacetates; Acids, Carbocyclic; Carboxylic Acids; Organic Chemicals; Piperidines

Study Officials

• Robert Noveck, MD, PhD

  Duke University

  PRINCIPAL INVESTIGATOR

• Ashwin Patkar, MD

  Duke University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: January 9, 2011
• First Posted: February 4, 2011
• Study Start: December 1, 2010
• Primary Completion: August 1, 2012
• Study Completion: August 1, 2012
• Last Updated: August 1, 2014

Record last verified: 2014-07

Locations

US (1)