Home
Search
Study Topics
Glossary
|
|
|
|
|
Sponsored by: |
Mutual Pharmaceutical Company, Inc. |
---|---|
Information provided by: | Mutual Pharmaceutical Company, Inc. |
ClinicalTrials.gov Identifier: | NCT00779259 |
In a prior in vitro study using human hepatocytes quinine was shown to induce the activity of Cytochrome p450 CYP
1A2. The present study will evaluate the extent to which quinine sulfate-related induction of this enzyme effects the pharmacokinetics of theophylline, a sensitive probe drug for the activity of CYP 1A2. It will also evaluate the effect of single-dose theophylline on the pharmacokinetics of steady-state quinine sulfate.
Condition | Intervention | Phase |
---|---|---|
Pharmacokinetics |
Drug: Theophylline 300mg Drug: Quinine 648 mg Drug: Theophylline 300 mg |
Phase I |
Study Type: | Interventional |
Study Design: | Basic Science, Non-Randomized, Open Label, Single Group Assignment, Pharmacokinetics Study |
Official Title: | A Pharmacokinetic Drug-Drug Interaction Study to Evaluate the Effect of Steady-State Quinine Sulfate on the Pharmacokinetics of Single-Dose Theophylline in Healthy Adult Males |
Enrollment: | 24 |
Study Start Date: | August 2007 |
Study Completion Date: | September 2007 |
Primary Completion Date: | September 2007 (Final data collection date for primary outcome measure) |
Arms | Assigned Interventions |
---|---|
Theophylline alone: Active Comparator
baseline theophylline pharmacokinetics
|
Drug: Theophylline 300mg
Single doses of theophylline 300 mg as an immediate-release oral solution 80mg/15ml concentration administered alone at 7 am on Day 1 after an overnight fast of at least 10 hours and along with quinine sulfate (2 x 324 mg capsules) at 7am on Day 12 after an overnight fast of at least 10 hours.
|
Quinine alone: Active Comparator
baseline quinine pharmacokinetics at steady state
|
Drug: Quinine 648 mg
648 mg quinine sulfate(2 x 324 mg capsules) initiated at 3pm on Day 5 and taken every 8 hours through Day 11 and co-administered with theophylline 300 mg as an immediate-release oral solution 80 mg/15 ml concentration at 7am on Day 12.
|
Theophylline with steady state quinine: Experimental
Theophylline pharmacokinetics in the presence of steady state quinine and quinine pharmacokinetics in the presence of theophylline.
|
Drug: Theophylline 300 mg
Single doses of theophylline 300 mg as an immediate-release oral solution 80mg/15ml concentration administered alone at 7 am on Day 1 after an overnight fast of at least 10 hours and along with quinine sulfate (2 x 324 mg capsules) at 7am on Day 12 after an overnight fast of at least 10 hours.
Drug: Quinine 648 mg
648 mg quinine sulfate(2 x 324 mg capsules) initiated at 3pm on Day 5 and taken every 8 hours through Day 11 and co-administered with theophylline 300 mg as an immediate-release oral solution 80 mg/15 ml concentration at 7am on Day 12.
|
This study will evaluate the effect of steady-state quinine sulfate on the pharmacokinetics of single dose theophylline and the effect of single dose theophylline on the pharmacokinetics of steady-state quinine sulfate in healthy adult males under fasting conditions. In this non-blinded, crossover study 24 normal, healthy, non-smoking, non-obese male volunteers will serve as their own controls in two cohorts, one consisting of 8 subjects and one consisting of 16 subjects. On Day 1 after a minimum overnight fast of 10 hours, the 8 study participants in cohort 1 will receive a single oral dose of theophylline (300 mg as an immediate-release oral solution 80 mg/ 15 ml concentration). After a 4 day washout period, the 8 subjects will receive a 648 mg dose of quinine sulfate (2 x 324 mg capsules) every 8 hours (dosing at 7 am, 3 pm and 11 pm daily) beginning with the 3 pm dose on Day 5 and continuing through the morning dose on Day 12. The 8 subjects will be co-administered single oral doses of theophylline (300 mg as an immediate-release oral solution 80 mg/ 15 ml concentration) and quinine sulfate (2 x 324 mg capsules) at 7 am on Day 12. Cohort 2 will be dosed on the basis of safety findings in Cohort 1. If ≥ 50% of the volunteers in cohort 1 do not tolerate the 648 mg dose of quinine sulfate, the second cohort of 16 volunteers will receive a dose of quinine sulfate reduced from 648 mg to 324 mg every 8 hours. In each cohort serial pharmacokinetic blood samples will be drawn at times sufficient to adequately define the pharmacokinetics of theophylline and quinine. Blood samples for the measurement of theophylline plasma concentrations will be collected on Days 1 and 12 prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 16, 24, 36 and 48 hours post-dose. Blood samples for the measurement of quinine sulfate plasma concentrations will be collected on Day 11 prior to the morning dose and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6, and 8 hours post dose and on Day 12 prior to dosing and at 0.5, 1, 1.5, 2, 2.5, 3, 4, 6 and 8 hours post-dose. A further goal of this study is to evaluate the safety and tolerability of this regimen in healthy volunteers.
Subjects will be monitored throughout participation in the study for adverse reactions to the study drug and/or procedures. Vital signs (sitting blood pressure and pulse) will be measured prior to the morning dose and at 1, 2 and 4 hours after administration of the morning dose on Days 1, 11 and 12. On Day 5, sitting blood pressure and pulse will be measured prior to the afternoon dose and at 1, 2 and 4 hours after administration of the afternoon dose. ECGs will be collected pre-dose and at 4 hours after the morning dose on study Days 1, 5, 11 and 12. All adverse events whether elicited by query, spontaneously reported or observed by clinic staff will be evaluated by the investigator and reported in the subject's case report form.
Ages Eligible for Study: | 18 Years to 45 Years |
Genders Eligible for Study: | Male |
Accepts Healthy Volunteers: | Yes |
Inclusion Criteria:
Exclusion Criteria:
United States, North Dakota | |
PRACS Institute | |
Fargo, North Dakota, United States, 58104 |
Study Chair: | Matthew Davis, MD | Mutual Pharmaceutical |
Principal Investigator: | Barrie March, MD | PRACS Institute |
Responsible Party: | Mutual Pharmaceutical Company, Inc. ( Vice President, Branded Products and Medical Affairs ) |
Study ID Numbers: | MPC-001-07-1002, R07-0738 |
Study First Received: | October 22, 2008 |
Results First Received: | May 27, 2009 |
Last Updated: | May 27, 2009 |
ClinicalTrials.gov Identifier: | NCT00779259 History of Changes |
Health Authority: | United States: Food and Drug Administration |
quinine sulfate theophylline drug interactions cytochrome p450 |
humans male adult drug interactions |
Anti-Infective Agents Vasodilator Agents Quinine Anti-Asthmatic Agents Healthy Cardiovascular Agents Antimalarials Phosphodiesterase Inhibitors |
Analgesics, Non-Narcotic Muscle Relaxants, Central Red Cinchona Peripheral Nervous System Agents Analgesics Bronchodilator Agents Theophylline |
Respiratory System Agents Anti-Infective Agents Vasodilator Agents Antiprotozoal Agents Molecular Mechanisms of Pharmacological Action Quinine Physiological Effects of Drugs Neuromuscular Agents Antimalarials Antiparasitic Agents Sensory System Agents Therapeutic Uses Muscle Relaxants, Central |
Analgesics Anti-Asthmatic Agents Enzyme Inhibitors Cardiovascular Agents Pharmacologic Actions Phosphodiesterase Inhibitors Autonomic Agents Analgesics, Non-Narcotic Peripheral Nervous System Agents Bronchodilator Agents Central Nervous System Agents Theophylline |