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MalariaPhase 1NCT01523002

Drug Interaction Study of Pyronaridine-artesunate & Metoprolol, & Redosing Study of Pyronaridine-artesunate

A Phase 1 study testing Metoprolol and pyronaridine-artesunate and pyronaridine-artesunate in people with Malaria, run by Medicines for Malaria Venture at 1 site in Switzerland.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

The primary objective of the drug-drug interaction study is to evaluate any drug interaction between the CYP2D6 substrate metoprolol and pyronaridine-artesunate in healthy volunteers. Read more about this study

Who is it for?
Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for
Malaria
What is being tested?
Metoprolol and pyronaridine-artesunate and pyronaridine-artesunate
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
56 participants
Where
1 siteSwitzerland
Study dates
Jan 2012to Oct 2012
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 55 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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
  • Signed and dated a written informed consent form before undergoing any study related activities
  • Medically normal subjects with no significant abnormal findings at the screening physical examination as evaluated by the investigator
  • Strictly normal values of alanine aminotransferase, aspartate aminotransferase, and total bilirubin and normal or abnormal and clinically insignificant results of the other blood and urine laboratory parameters at screening.
  • 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)
  • 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:
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  • 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
  • The ability to understand the requirements of the study and willingness to comply with all study procedures

Who cannot join

  • Known history or evidence of clinically significant disorders such as cardiovascular (including arrhythmia, acute corrected QT interval greater or equal to 450 milliseconds), 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)
  • Known history of hypersensitivity, allergic or adverse reactions to pyronaridine or artesunate or other artemisinins or metoprolol.
  • Other contraindications to pyronaridine use
  • 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.
  • Known active Hepatitis A IgM (HAV-IgM), Hepatitis B surface antigen (HBsAg) or Hepatitis C antibody (HCV Ab)
  • Seropositive HIV antibody
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  • Previous participation in any clinical study with pyronaridine:artesunate (Pyramax)
  • Presence or recent history (last two years) of tobacco abuse (≥10 cigarettes/day)
  • Known or suspected alcohol abuse or illicit drug use 10 years before the study start or positive findings on urine drug screen
  • 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
  • Gilbert's disease
  • 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.
  • Plasma donation 3 months before the study start
  • Blood donation of 500 mL or more 3 months before the study start
  • Participation in any clinical study in last 3 months

Trial locations and contacts

1 site in 1 country.

Switzerland1 site
  • Covance Clinical Research Unit AG

    Allschwil, Basel, 4123

Other trials in Switzerland

About this study

Official title: Open-label, Drug Interaction Study of Pyronaridine-artesunate and Metoprolol in Healthy Volunteers and Pyronaridine-artesunate Redosing Study in Healthy Volunteers

The primary objective of the drug-drug interaction study is to evaluate any drug interaction between the CYP2D6 substrate metoprolol and pyronaridine-artesunate in healthy volunteers.

The primary objective of the pyronaridine-artesunate redosing study is to determine the safety of redosing a 3-day regimen of pyronaridine-artesunate following 60 or 90 days in healthy volunteers.

Read the detailed description

This was a phase I, open-label, randomised, 2-arm parallel group study in healthy subjects. The study population will include 44 healthy subjects (22 per treatment arm), comprising male and female adults (18-55 years) of any ethnic origin.

Subjects will be randomised to either Arm A or Arm B. Arm A will evaluate pyronaridine-artesunate interference on metoprolol pharmacokinetics (PK) and the effect of a 90-day (±7 days) redosing interval on the safety profile of pyronaridine-artesunate. Arm B will evaluate the effect of a 60-day (±7 days) redosing interval on the safety profile of pyronaridine-artesunate.

Screening will be performed in the 14-day period prior to the first dose. In Arm A, each subject will partake in 3 inpatients periods between: Days -1 to 2, Days 7 to 11, and Days 97 to 101, with dosing on Days 1, 8 to 10, and 98 to 100. In Arm B, each subject will partake in 2 inpatient periods: Days -1 to 4 and Days 60 to 64, with dosing on Days 1 to 3 and 61 to 63. 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.

Conditions
Malaria
Being tested
Metoprolol and pyronaridine-artesunate, pyronaridine-artesunate
Keywords
pyronaridine artesunate (Pyramax), artemisinin based combination therapy (ACT), metoprolol, drug-drug interaction study, redosing study
Medical subject headings
Malaria

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Metoprolol and pyronaridine-artesunateDrug

    On Day 1, subjects will receive a single oral 100 mg dose of metoprolol tartrate. On Day 8 and Day 9, subjects will receive a once daily oral dose of pyronaridine-artesunate as follows:

    55 - < 65 kg: 3 tablets (180:60 mg pyronaridine:artesunate)

    ≥ 65 kg: 4 tablets (180:60 mg pyronaridine:artesunate)

    On Day 10, a 100 mg dose of metoprolol will be coadministered with pyronaridine-artesunate at the above dose.

    On Days 98 - 100, subjects will receive pyronaridine-artesunate once daily at the same dose described above. Followed by a 40 day follow-up period.

  • pyronaridine-artesunateDrug

    Also called Pyramax

    On Days 1 to 3, subjects will receive 3 days of pyronaridine-artesunate as follows:

    55 - < 65 kg: 3 tablets (180:60 mg pyronaridine:artesunate)

    ≥ 65 kg: 4 tablets (180:60 mg pyronaridine:artesunate)

    On Days 61 to 63, subjects will be redosed with a 3 day course of pyronaridine-artesunate at the above dose.

    Followed by a 40 day follow-up period.

Study groups in NCT01523002
Study groupRoleWhat they receive
Arm A: metoprolol and pyronaridine-artesunate 90-day redosingActive comparatorSubjects will take 1 day of metoprolol followed by a 7 day wash out period, then 2 days of pyronaridine-artesunate followed by 1 day of pyronaridine-artesunate + metoprolol, followed by a 87 day follow-up period. Subjects will then receive pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.
Receives: Drug: Metoprolol and pyronaridine-artesunate
Arm B: pyronaridine-artesunate 60-day redosingActive comparatorSubjects will take pyronaridine-artesunate once daily for 3 days, followed by a 57 day follow-up period. Subjects will then take pyronaridine-artesunate once daily for 3 days followed by a 40 day follow-up period.
Receives: Drug: pyronaridine-artesunate

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Arm A Pharmacokinetic Parameters of Metoprolol & α-hydroxymetoprolol: Area Under Curve (AUC)0-t, AUC0-∞

    AUC0-t \& AUC0-∞ of Metoprolol \& α-hydroxymetoprolol for Period 1 (metoprolol alone) \& Period 2 (pyronaridine-artesunate with metoprolol)

    Abbreviations: AUC = area under the concentration-time curve; AUC0-t = AUC from Hour 0 to the last quantifiable concentration time (LQCT), where LQCT is the time at which the last sample with a quantifiable concentration was drawn; AUC0-∞ = AUC from Hour 0 to infinity

    Measured: Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10

  2. Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: Tmax

    tmax of Metoprolol \& α-hydroxymetoprolol for Period 1 (metoprolol alone) \& Period 2 (pyronaridine-artesunate with metoprolol)

    Abbreviations: tmax = time to maximum observed concentration.

    Measured: Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10

  3. Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: t1/2

    t1/2 of Metoprolol \& α-hydroxymetoprolol for Period 1 (metoprolol alone) \& Period 2 (pyronaridine-artesunate with metoprolol)

    Abbreviations: t1/2 = apparent terminal phase half-life

    Measured: Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10

  4. Arm A Pharmacokinetics Parameters of Metoprolol & α-hydroxymetoprolol: Cmax

    Cmax of Metoprolol \& α-hydroxymetoprolol for Period 1 (metoprolol alone) \& Period 2 (pyronaridine-artesunate with metoprolol)

    Abbreviations: Cmax = maximum peak observed concentration

    Measured: Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10

  5. World Health Organization (WHO) Treatment Emergent Adverse Events

    To assess the safety of redosing a 3-day regimen of pyronaridine-artesunate. Grade 1: mild adverse event Grade 2: moderate adverse event Grade 3: severe and undesirable adverse event Grade 4: life threatening adverse event Grade 5: fatal adverse event resulting in death

    Measured: 140 days

  6. Non-WHO Listed Treatment Emergent Adverse Events

    To assess the safety of redosing a 3-day regimen of pyronaridine-artesunate

    Measured: 140 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Feb 2012 (estimated)
  2. Study startJan 2012
  3. Primary completionJul 2012
  4. Study completionOct 2012

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
56 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01523002
Sponsor's protocol ID
SP-C-014-11
Status last verified
Dec 2023
First submitted
27 Jan 2012
Last updated
14 Dec 2023
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Metoprolol and pyronaridine-artesunate and pyronaridine-artesunate in people with Malaria, run by Medicines for Malaria Venture at 1 site in Switzerland.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 9 inclusion and 15 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 14 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 14 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Arm A Pharmacokinetic Parameters of Metoprolol & α-hydroxymetoprolol: Area Under Curve (AUC)0-t, AUC0-∞ (time frame: Plasma samples taken predose and following metoprolol dosing at 0.25, 0.5, 0.75, 1, 1.5, 2, 3, 4, 6, 8, 10, 12 and 24 hours postdose on Days 1 & 10). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Dec 2023.

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