A comparative assessment of two lumefantrine formulations compared to the standard reference formulation in healthy male and female volunteers of non-childbearing potential.
A two-period, open-label, randomized, parallel-group, partial cross-over study to evaluate the relative bioavailability and pharmacokinetics of two lumefantrine formulations in comparison to a reference formulation in healthy volunteers
Novartis Pharmaceuticals Corporation
60 participants
Oct 1, 2018
Interventional
Conditions
Summary
The reason for this study is to find out which of these two new versions of lumefantrine is better absorbed into the body of healthy volunteers. The purpose of this study is to explore: • Whether there is a similarity between how Formulation 1, Formulation 2 and LUM-SDF are absorbed by the body by healthy volunteers • Whether there is a similarity between how Formulation 1, Formulation 2 and LUM-SDF affects your body with healthy volunteers • Safety and Tolerability of Formulation 1 and Formulation 2 when compared to LUM-SDF in healthy volunteers.
Eligibility
Inclusion Criteria11
- Written informed consent must be obtained prior to participation in the study.
- Healthy male and female subjects of non-childbearing potential aged 18 to 55 years included, and in good health as determined by past medical history, physical examination, vital signs, ECG, and laboratory tests at Screening.
- At Screening, vital signs (systolic and diastolic blood pressure and
- pulse rate) will be assessed in the sitting position after the subject has rested for at least 5 minutes, and again after 3 minutes in the standing position at Screening only. Sitting vital signs will be captured for the duration of the study and should be within the normal range:
- oral body temperature between 35.0°C to 37.5°C
- systolic blood pressure, 90 to 139 mmHg
- diastolic blood pressure, 40 to 89 mmHg
- pulse rate, 40 to 90 bpm
- Subjects must weigh at least 50 kg to participate in the study, and must have a body mass index (BMI) within the range of 18 to 30 kg/m2. BMI = body weight (kg)/(height [m])2.
- Able to communicate well with the Investigator, to understand and
- comply with the requirements of the study.
Exclusion Criteria9
- Women of childbearing potential, defined as all women physiologically capable of becoming pregnant. Women are considered postmenopausal and not of childbearing potential if they have had 12 months of natural (spontaneous) amenorrhea with an appropriate clinical profile (e.g., age appropriate history of vasomotor symptoms) or have had surgical bilateral oophorectomy (with or without hysterectomy), total hysterectomy or tubal ligation at least 6 weeks ago. In the case of oophorectomy alone, a woman will only be considered not of childbearing potential if her reproductive status has been confirmed by follow-up hormone level assessment.
- Pregnant or nursing (lactating) women, where pregnancy is defined as the state of a female after conception and until the termination of gestation, confirmed by a positive human chorionic gonadotropin laboratory test.
- Sexually active males unwilling to use a condom during intercourse or unwilling to refrain from sperm donation for greater than or equal to 4 weeks (28 days) after last dosing. A condom is required for all sexually active male participants to prevent them from either fathering a child OR donating sperms.
- Use of any prescription drugs or over-the-counter medication (vitamins, herbal supplements, and dietary supplements) within 4 weeks or 5 times the terminal half-life of each drug prior to dosing.
- Use of other investigational drugs at the time of enrollment, or within
- days, whichever is longer; or longer if required by local regulations.
- History of hypersensitivity to the study drug or any of its excipients or to drugs of similar chemical classes.
- A past medical history of clinically significant cardiac or ECG
- abnormalities (including arrhythmias) or a family history (grandparents, parents and siblings) of a prolonged QT interval syndrome, defined as a corrected QT interval, by Fridericia formula of > 450 msec of males and > 460 msec for females at Screening or first Baseline.
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Interventions
A two-period, open-label, parallel-group and partial cross-over study to evaluate the safety, tolerability and PK of two lumefantrine (LUM) formulations in comparison to a reference formulation. In Period 1, the PK of the LUM formulations will be compared to the SDF. After an internal review of the results in Period 1, Period 2 will evaluate the effect of a standard African meal and 250mls of whole milk on the bioavailability of the SDF at a single dose (480 mg). Period 1: Following a 28-day screening period, and Day -1 baseline assessments, eligible subjects will be randomized to receive one of three treatments administered as an oral sachet: lumefantrine (LUM) Standard Reference Formulation (480mg), LUM Formulation 1 (480 mg), LUM Formulation 2 (480mg). Day 1 predose assessments will be collected in the morning and once eligibility is confirmed the subjects will receive a single oral dose of the assigned study medication. Subjects will be domiciled up to 24 hours postdose with safety and sequential PK samples collected during the 24 hours. Subjects will return to the study center on Days 3, 5, 8, 10, 12 for PK sample collections. End of treatment assessments will take place on Day 14 when the subjects return to the clinic. Period 2: Subjects who complete Period 1 will be asked to return for Period 2. New replacement subjects will be allowed to enter Period 2 in the event there are insufficient subjects returning from Period 1. After a minimum 4 week washout period, subjects from Period 1 who agree and meet eligibility will continue in Period 2. 6 subjects, have received a single dose of the SDF with standard African meal and up to 12 subjects will receive a single dose of SDF and 250mls of whole milk. Day 1 predose assessments will be collected in the morning and once eligibility is confirmed the subjects will receive a single oral dose of the assigned study medication. Subjects will be domiciled up to 24 hours postdose with safety and sequential PK samples collected during the 24 hours. Subjects will return to the study site on Days 3, 5, 8, 10, 12 for PK collections. End of study assessments will take place on Day 14 or when the subjects return to the clinic. At the time of this update, six subjects returned from the recruited 30 in Period 1 into Period 2. All six subjects entered Treatment Group 6. As a result, replacement subjects will be enrolled into Period 2, Treatment Group 7 following a 28 day screening period, and Day 1 baseline assessments.
Locations(1)
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ACTRN12618000968279