Comparative Bioavailability of Dronabinol Oral Solution Versus Branded Capsule 5 mg Under Fasting Conditions

A Single-Dose, Replicate Crossover Design Comparative Bioavailability Study of Dronabinol Oral Solution 5 mg Versus Marinol Capsules 5 mg Under Fasted Conditions

This is a comparative study to assess bioavailability of a proposed alternate dosage form against the current FDA-approved branded product.

Study Overview

• Status: Completed
• Conditions: Bioavailability
• Intervention / Treatment: Drug: Dronabinol Capsules, 5 mg; Drug: Dronabinol Oral Solution

• Study Type: Interventional
• Enrollment (Actual): 88
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Texas
    • Austin, Texas, United States, 78754
      • Worldwide Clinical Trials Drug Development Solutions

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Male and female healthy subjects between 18 and 55 years of age, inclusive.
2. Subjects must have a body mass index (BMI) within 19 and 29.9 kg/m2, inclusive and weigh a minimum of 50 kg (110 pounds).
3. Subjects must be in general good health as determined by medical history, physical examination, or laboratory evaluations conducted at the screening visit and upon admission to the clinic. Examination should include a thorough examination of oral cavity for any abnormal findings.
4. Subjects must be non-smokers, defined as not having used any tobacco products in the past six months. Negative results from a urine cotinine test conducted at Screening.
5. Subjects must be able to provide informed consent after risks and benefits have been explained, and be willing to comply with study procedures.
6. Female subjects of childbearing potential must not be pregnant or nursing; and must be surgically sterile; one year postmenopausal; or on hormonal contraceptive agent(s), diaphragm or condom with spermicidal foam or jelly, or IUD for at least three months prior to drug administration and agree to use the same method of contraception for at least one month after the last drug administration.
7. Negative urine pregnancy test at screening and prior to drug administration of each period.
8. Negative HIV 1, hepatitis C virus (HCV) antibody, hepatitis B surface antigen within 30 days prior to the start of the study.
9. Negative results from screening for drugs of abuse at Screening and Day-1 (check-in) prior to drug administration during all study periods.

Exclusion Criteria:

1. Known hypersensitivity or allergy to dronabinol, Marinol, marijuana, hashish, or sesame oil.
2. Have participated in an investigational trial within 30 days or six half-lives of the test drug's biologic activity, whichever is longer, before the time of first study dose in this study.
3. Presence of visible signs of an infection, mucositis, cold sores, lesions, local irritation, periodontal disease of the oral cavity or any abnormal finding in the oral cavity. In addition, evidence of piercings of the tongue, lip, or anywhere in the oral cavity or a history of oral cavity piercings.
4. Have donated or received blood or blood products within 30 days prior to the first study dose.
5. Have received any prescription drug (excluding hormonal contraceptives) within 14 days of study drug administration, over-the-counter drugs within seven days of study drug administration, and/or vitamins or herbal supplements within three days of study drug administration.
6. Significant bradycardia or tachycardia defined as having a resting heart rate <45 bpm or >100 bpm, respectively.
7. Clinical evidence of either hypotension (defined as systolic blood pressure <90 mmHg or diastolic blood pressure <50 mmHg), or hypertension (defined as systolic blood pressure >139 mmHg or diastolic blood pressure >89 mmHg).
8. Any history of clinically significant organ system (cardiovascular, neurological, hepatic, hematopoietic, renal, pulmonary, endocrine, or gastrointestinal) disorders or ongoing infectious diseases; or any other conditions that might interfere with the absorption, distribution, metabolism or excretion of the study drug, or that would place the subject at increased risk.
9. Use of marijuana (directly or indirectly) within 90 days prior to drug administration and during the course of the study.
10. History of treatment for alcohol abuse, significant mental illness, physical dependence to any opioid, barbiturates, amphetamines, cocaine, or benzodiazepines in the past 10 years.

Study Plan

How is the study designed?

Design Details

• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Marinol	Drug: Dronabinol Capsules, 5 mg; Comparison of different routes of administration of a drug using the approved Abbott 5 mg capsule product under fasting conditions; two treatment periods with a washout period separating the study periods
EXPERIMENTAL: oral solution	Drug: Dronabinol Oral Solution; Comparison of different routes of administration of a drug using a proposed oral solution formulation under fasting conditions; two treatment periods with a washout period separating the study periods

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate and extent of absorption	The plasma concentration versus time data of dronabinol and its metabolite (11-hydroxy-delta-9-tetrahydrocannabinol) will be analyzed. The PK parameters Cmax, AUC0-t and AUCinf for delta-9-tetrahydrocannabinol will be calculated and used as the measures for comparative bioavailability assessment of dronabinol oral solution versus the innovator capsule product.	48 hours

Collaborators and Investigators

• Sponsor: INSYS Therapeutics Inc
• Investigators: Principal Investigator: Joe Juren, M.D., Worldwide Clinical Trials

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (ACTUAL): December 1, 2011
• Study Completion (ACTUAL): December 1, 2011

Study Registration Dates

• First Submitted: October 5, 2011
• First Submitted That Met QC Criteria: October 6, 2011
• First Posted (ESTIMATE): October 7, 2011

Study Record Updates

• Last Update Posted (ESTIMATE): March 26, 2012
• Last Update Submitted That Met QC Criteria: March 23, 2012
• Last Verified: March 1, 2012

More Information

Terms related to this study

• Keywords: Dronabinol; fasting
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Analgesics, Non-Narcotic; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Psychotropic Drugs; Hallucinogens; Cannabinoid Receptor Agonists; Cannabinoid Receptor Modulators; Dronabinol
• Other Study ID Numbers: INS-10-012