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Drug Interaction Study of Pyronaridine-artesunate and Metoprolol and Pyronaridine-artesunate Re-dosing Study in Healthy Volunteers

Information source: Medicines for Malaria Venture
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Malaria

Intervention: Metoprolol and Pyronaridine : artesunate (Drug); pyronaridine:artesunate (Drug)

Phase: Phase 1

Status: Completed

Sponsored by: Medicines for Malaria Venture

Official(s) and/or principal investigator(s):
Rolf Pokorny, MD, MSc, Principal Investigator, Affiliation: Covance Research Unit AG

Summary

Pyronaridine: artesunate (Pyramax) is an antimalarial fixed-dose combination therapy which has been demonstrated to be well tolerated and effective treatment in patients with Plasmodium falciparum and vivax malaria. This open-label Phase I study has two parts: a drug-drug interaction part intended to investigate the interaction of Pyramax in the pharmacokinetics of the CYP2D6 probe metoprolol and a re-dosing evaluation part intended to investigate the differences on the changes in liver enzymes induced by Pyramax in a first and in a second treatment course and the effect of the redosing interval on the changes in liver enzymes induced by Pyramax in a first and in a second treatment course.

Clinical Details

Official title: Open-label, Drug Interaction Study of Pyramax (Pyronaridine:Artesunate) and Metoprolol in Healthy Volunteers and Pyramax Re-dosing Study in Healthy Volunteers

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

Primary outcome:

Profile of Pharmacokinetics

Safety of re-treatment

Detailed description: Healthy subjects will be randomised to either arm A (sequential metoprolol single dose and Pyramax 3 days course + metoprolol on the last day starting 7 days after Pyramax single dose followed by Pyramax redosing with another 3 days course 90 days later) or arm B (2 courses of 3-days Pyramax separated by 60 days). Each arm will include 22 subjects. Subjects will be followed for tolerability and pharmacokinetics for 42 days following each start of Pyramax dosing period. Subjects will be considered to have completed the study at Day 140 (arm A) or at Day 103 (arm B). Any adverse event ongoing at the time of study completion will be followed until resolution unless no further change is expected according to the investigator.

Eligibility

Minimum age: 18 Years. Maximum age: 55 Years. Gender(s): Both.

Criteria:

Inclusion Criteria: 1. Male or female subjects between the ages of 18 and 55 years with a body weight

between 50 and 90 kg and a body mass index calculated using Quetelet's Index - weight

(kg)/height2 (m2) between 18. 5-30. 0 2. Signed and dated a written informed consent form before undergoing any study related activities 3. Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the investigator 4. Strictly normal values of ALT, AST, and total bilirubin and normal or abnormal and clinically insignificant results of the other blood and urine laboratory parameters at screening. 5. Female subjects of non-childbearing potential (i. e., physiologically incapable of becoming pregnant, including any female who was post-menopausal (i. e., one year without menses) or who has undergone sterilization (via hysterectomy or bilateral tubal ligation) 6. Female subjects of childbearing potential with a negative urine pregnancy test at

screening confirmed at Day - 1 by a serum pregnancy test and who agreed to one of the

following methods:

- Double barrier method of contraception for 2 weeks before first study drug

administration and throughout the entire study follow up period

- Partner(s) who had undergone vasectomy and has been negative for sperm for at

least 6 months 7. The ability to understand the requirements of the study and willingness to comply with all study procedures Exclusion Criteria: 1. Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, acute QTc interval greater or equal to 450 mseconds), respiratory (including active tuberculosis), hepatic, renal, gastrointestinal, immunological (including active HIV-AIDS), neurological (including auditory), endocrine, infectious, malignancy, psychiatric or other abnormality (including head trauma) 2. Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins or metoprolol. 3. Other contraindications to pyronaridine use 4. Other contraindications to metoprolol use including second or third degree atrioventricular block, heart rate below 50 beats per minute, uncompensated heart failure or need for treatment with inotropic agents, clinically apparent hypotension, sinus bradycardia or sick sinus syndrome, peripheral arterial disease, pheochromocytoma, asthma, chronic obstructive pulmonary disease, depression and any other condition with in the opinion of the Investigator may be worsened by administration of metoprolol. 5. Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab) 6. Seropositive HIV antibody 7. Previous participation in any clinical study with pyronaridine: artesunate (Pyramax) 8. Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day) 9. Known or suspected alcohol abuse or illicit drug use 10 years before the study start or positive findings on urine drug screen 10. Intake of alcoholic beverages within 72 hours before study drug administration or caffeine-containing food or beverages, such as coffee, tea, chocolate, or cola, 48 hours before study drug administration 11. Gilbert's disease 12. Administration of any systemic medication or herbal product within 14 days before the first dose of study drug. If the investigator considers that the specific product would not interfere with the safety of the subject or the objectives of the study, topical treatments as well as vitamins and mineral supplements not containing other substances are allowed until 4 days before each dose. Ibuprofen at doses of at most 1200 mg per day for no more than 3 consecutive days or 6 non-consecutive days is allowed until 24h before the first dose of study drug. 13. Plasma donation 3 months before the study start 14. Blood donation of 500 mL or more 3 months before the study start 15. Participation in any clinical study in last 3 months

Locations and Contacts

Covance Clinical Research Unit AG, Allschwil, Basel 4123, Switzerland
Additional Information

Starting date: January 2012
Last updated: January 25, 2013

Page last updated: August 23, 2015

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