Fed Study of Chlorpheniramine Polistirex and Hydrocodone Polistirex Capsules and Tussionex® Pennkinetic® Extended Release Oral Suspension

An Open-Label, Randomized, Two-Period, Crossover Study to Evaluate the Bioequivalence of an Extended Release Test Capsule Formulation of Chlorpheniramine Polistirex and Hydrocodone Polistirex Compared to an Equivalent Dose of a Commercially Available Reference Drug Product (Tussionex® Pennkinetic® Extended Release Oral Suspension, Celltech Pharmaceuticals, Inc.) in Normal Human Subjects Under Fed Conditions

The objective of this open-label, randomized, two-period, crossover study was to evaluate the oral bioavailability of the Mallinckrodt extended release test capsule formulation of chlorpheniramine polistirex/hydrocodone polistirex compared to an equivalent oral dose of a commercially available extended release oral suspension of chlorpheniramine polistirex/hydrocodone polistirex (Tussionex® Pennkinetic® Extended Release Oral Suspension, Celltech Pharmaceuticals, Inc.) in a test group of healthy subjects under fed conditions.

Study Overview

• Status: Completed
• Conditions: Healthy
• Intervention / Treatment: Drug: Chlorpheniramine polistirex equivalent to 8 mg of chlorpheniramine maleate and hydrocodone polistirex equivalent to 10 mg of hydrocodone bitartrate capsule; Drug: 5 mL chlorpheniramine (8 mg/5 mL)/hydrocodone (10 mg/5 mL) extended release oral suspension

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Missouri
    • St. Charles, Missouri, United States, 63301
      • Gateway Medical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Males or non-pregnant, non-lactating females, 18 years of age or older.
2. Female subjects must be postmenopausal for at least one year, or surgically sterile, or practicing adequate non-hormonal contraception for at least 3 months prior to and for the duration of study participation. All female subjects will undergo a pregnancy test at screening and at check-in to the clinical study site for every dosing period. The results of the test must be negative for continued participation.
3. Weight must be within 15% of the ideal weight for height and frame, as adopted by the Metropolitan Life Insurance Co., 1993.
4. Qualifying subjects must be in good health and physical condition as determined by a screening medical history obtained within 30 days prior to study start. Subjects should not present with a history of significant past illness expected to affect the investigation.

5. The normal status of subjects will be confirmed by the following procedures:

   1. Laboratory tests (chemistry, hematology, urinalysis)
   2. Human immunodeficiency virus (HIV), hepatitis, alcohol, and "drugs of abuse" testing will be done for screening purposes only. Results of the HIV, hepatitis, and "drugs of abuse" tests must be negative or non-reactive for subjects to qualify for the study.
   3. Electrocardiogram: A 12-lead electrocardiogram (ECG) will be obtained for all subjects. This ECG must be interpreted by appropriately trained and experienced medical personnel. A subject with an ECG that is not within normal range does not qualify, unless specifically accepted (with comment) by the investigator.
6. Subjects must be able to provide written consent and agree to abide by the study requirements (including consuming the entire standardized breakfast).

Exclusion Criteria:

1. History of chronic alcohol, drug, or narcotic abuse.
2. Chronic use of tranquilizers, sedatives, aspirin, antibiotics, or other medications.
3. History or presence of major organ dysfunction.
4. History of malignancy, stroke, or diabetes; cardiac, renal, liver, pulmonary, or severe gastrointestinal disease; or other serious illness.
5. History of anxiety, tension, severe agitation, psychosis, or mental depression.
6. Family history or diagnosis of epilepsy or other seizure disorder.
7. History of glaucoma.
8. History of acute abdominal conditions.
9. History of conditions which might contraindicate or require caution be used in the administration of chlorpheniramine/hydrocodone, including: history of renal impairment, hepatic or biliary tract disease, inflammatory bowel disease, ulcerative colitis, constipation, diarrhea, gastrointestinal obstruction or ileus, cardiac disease, hypertension, bladder obstruction, pain or difficulty passing urine, systemic lupus erythematosus, head trauma, increased intracranial pressure, pulmonary disease, asthma, or history of hypersensitivity to any opiate agonists or antihistamines.
10. Administration of any other investigational drug during the 30 days prior to enrollment into the study.
11. Subjects who smoke or have a history of smoking, or use nicotine-containing products.
12. Subjects who have donated blood within 30 days prior to study entry, including that withdrawn during the conduct of any other clinical study.
13. Subjects presenting with acute illness.
14. Subjects who must wear contact lenses during the study.
15. Subjects who have taken prescription drugs within 14 days or over-the-counter medications (including herbal preparations) within 7 days prior to dosing except for standard daily dose multivitamins.

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
EXPERIMENTAL: A; Chlorpheniramine polistirex/hydrocodone polistirex extended release capsule	Drug: Chlorpheniramine polistirex equivalent to 8 mg of chlorpheniramine maleate and hydrocodone polistirex equivalent to 10 mg of hydrocodone bitartrate capsule; Chlorpheniramine polistirex/hydrocodone polistirex extended release capsule, single dose with food
ACTIVE_COMPARATOR: B; Tussionex® Pennkinetic® Extended Release Oral Suspension	Drug: 5 mL chlorpheniramine (8 mg/5 mL)/hydrocodone (10 mg/5 mL) extended release oral suspension; Tussionex® Pennkinetic® Extended Release Oral Suspension, single dose with food

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bioequivalence based on AUCf, AUCinf and Cmax	Two-period crossover with blood samples obtained prior to and following each dose at selected times through 72 hours. Washout period between doses was 7 days.

Collaborators and Investigators

• Sponsor: Mallinckrodt

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Primary Completion (ACTUAL): October 1, 2003
• Study Completion (ACTUAL): October 1, 2003

Study Registration Dates

• First Submitted: February 26, 2009
• First Submitted That Met QC Criteria: February 27, 2009
• First Posted (ESTIMATE): March 2, 2009

Study Record Updates

• Last Update Posted (ESTIMATE): October 19, 2016
• Last Update Submitted That Met QC Criteria: October 18, 2016
• Last Verified: October 1, 2016

More Information

Terms related to this study

• Keywords: Healthy Subjects
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Dermatologic Agents; Analgesics, Opioid; Narcotics; Respiratory System Agents; Anti-Allergic Agents; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Antitussive Agents; Chlorpheniramine; Hydrocodone
• Other Study ID Numbers: 8867-03-791