Single Dose Trial of Extended Release Combination Tablet Codeine and Guaifenesin

Cough Clinical Trial

Official title:

An Open-Label, Single-Dose, Crossover Comparative Bioavailability and Pharmacokinetic Study of Codeine Phosphate/Guaifenesin Extended-Release Tablet With Immediate-Release Tablet

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02157649
• Other study ID #: COGU506
• Status: Completed
• Phase: Phase 1
• First received: June 4, 2014
• Last updated: April 14, 2015
• Start date: June 2014
• Est. completion date: September 2014

Study information

• Verified date: April 2015
• Source: Nexgen Pharma, Inc
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

The objectives of this study are (a) to determine if drug levels from a single dose of an extended-release Codeine/Guaifenesin tablet are similar to an immediate-release tablet given every four hours containing lower doses considered safe for over-the-counter use; (b) to evaluate if food affects the drug levels of this extended-release Codeine/Guaifenesin tablet after a single administration; and (c) to assess the safety and tolerability of the Codeine/Guaifenesin extended-release and immediate release tablet formulations.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 26
• Est. completion date: September 2014
• Est. primary completion date: August 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 45 Years

Eligibility

Inclusion Criteria:

• Healthy non-smoking volunteers (Female volunteers on a stable contraceptive medication regimen (> 3 months) may continue during the course of the study but its use must be documented), 18 to 45 years of age, inclusive; Ethnic Group: Arab & Mediterranean.

• Race: Mixed skin (white & black skin people).

• Body Mass Index (BMI) between 18 and 32 kg/m2, inclusive;

• willing and able to comply with the appropriate instructions necessary to complete the study, and;

• Fully informed of the risks of entering the study and willing to provide written informed consent.

• Subject is available for the whole study period and gave written informed consent

• If female, must be practicing abstinence or using a medically acceptable form of contraception (e.g., intrauterine device, hormonal birth control [continuously used for at least 3 months before first dose], or double barrier method). For the purpose of this study, all females are considered to be of childbearing potential unless they have been post - menopausal, biologically sterile, or surgically sterile (i.e., hysterectomy, bilateral oophorectomy, or tubal ligation) for more than one (1) yearNormal Physical examination.

• Vital signs within normal ranges.

• All laboratory screening results within the normal range, or being assessed as clinically Non-significant by the attending physician.

• Normal Kidney and Liver functions test.

Exclusion Criteria:

• Women of childbearing potential who don't use any contraceptive method, pregnant and/or lactating women.

• Ethnic Group (Non- Arab &/ or Non- Mediterranean)

• A significant abnormality in the pre-study physical examination that would place the volunteer at risk during participation in the trial;

• A clinical laboratory test value outside of the accepted reference range that is deemed by the Investigator to be clinically significant;

• Require prescription medication on a regular basis;

• A clinically significant illness during the 28 days prior to Period 1 dosing (as determined by the Investigator);

• History of serious illness that can impact fate of drugs

• History of gastrointestinal obstruction, constipation, inflammatory bowel disease, gallbladder disease, pancreas disorder over last 2 years, or recent (over last 3 years) gastrointestinal tract surgery, including gall bladder resection;

• Known history or presence of cardiac, pulmonary, endocrine, musculoskeletal, neurological, hematological or disease.

• Subjects with acute pulmonary insufficiency, respiratory depression, acute or chronic severe respiratory insufficiency or history of any of these

• History of head injury, seizures over last 4 years deemed by the Investigator to be clinically significant;

• Mental disease

• History of kidney disease or urination problem over last 2 years deemed by the Investigator to be clinically significant

• Subjects with renal and/or hepatic insufficiency should be excluded

• Presence of any significant physical or organ abnormality

• History of low blood pressure is deemed by the Investigator to be clinically significant;

• A positive Hepatitis B surface antigen, Hepatitis C antibody screen, or a reactive HIV antibody screen;

• Known or suspected hypersensitivities, allergies, or other contraindications to Codeine or a related opioid and/or Guaifenesin;

• History of severe allergy or allergic reactions to study drug or related drugs or heparin

• Known history or presence of food allergies, or any condition known to interfere with the absorption, distribution, metabolism or excretion of drugs

• Known or suspected history of drug abuse within lifetime as judged by the Investigator;

• History of alcohol abuse or excessive intake of alcohol within last 5 years as judged by the Investigator;

• Positive screen for drugs of abuse, alcohol, or cotinine (nicotine) at screening or on admission to the unit prior to administration of investigational products;

• Use of drugs that induce or inhibit the hepatic metabolizing cytochrome P450 2D6 enzymes, within 30 days prior to administration of study formulations. Examples of inducers include: piperidins, carbamazepine, dexamethasone, rifampin. Examples of inhibitors include: cimetidine, diphenhydramine, fluvastatine, methadone, and ranitidine;

• Use of prescription medications within 21 days and OTC medications (including vitamins or herbal products) within 7 days (excluding flu vaccination) prior to the first administration of the study medication without Sponsor approval;

• Intake of Alcohol, caffeine, or xanthine beverages 16 hrs before each study drug administration.

• Use of any investigational drug within 30 days prior to first dosing;

• Use of any tobacco-containing product within 6 months of first dosing;

• Donated more than 400 mL of blood within 4 weeks before first dosing;

• Participation in another bioequivalence study and/or Clinical trials within 80 days prior to the start of this study Period I

• Exhausting physical exercise in the last 48 hours (e.g. weight lifting) or any recent significant change in dietary or exercise habits.

• Abnormal vital signs

• Abnormal Kidney and Liver functions test.

• In the opinion of the Investigator, unlikely or unable to successfully complete the study;

• Volunteer is vegetarian.

• Vomiting, Diarrhea on admission.

Study Design

Allocation: Randomized, Endpoint Classification: Pharmacokinetics Study, Intervention Model: Crossover Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cough

Intervention

Drug:
• IR Tablet under Fasted conditions
Administration of IR Tablets combination of Codeine Phosphate/Guaifenesin 20mg/400mg every 4 hours for 12 hours total.
• ER Tablet under Fed Conditions
Administration of two ER Tablet combination of Codeine Phosphate/Guaifenesin 30mg/600mg
• ER Tablet under Fasted Conditions
Administration of two Codeine Phosphate/Guaifenesin 30mg/600mg ER Tablets under fasted conditions.

Locations

Country	Name	City	State
Jordan	Pharmaceutical Research Unit	Amman

Sponsors (1)

Lead Sponsor	Collaborator
Nexgen Pharma, Inc

Country where clinical trial is conducted

Jordan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum Levels of Codeine and Guaifenesin	Blood samples drawn prior to dosing with tablets, then at 19 additional time points over the next 24 hours.	20 samples over 24 hours	No
Secondary	Safety and Tolerability	Collect adverse event data during the dosing and sampling intervals	24 hours	Yes