Bioequivalence
Conditions
Keywords
CHILD-IVITAB, STROMECTOL, Ivermectin, Palatability
Brief summary
This is a phase I, single-center, open-label, randomized, two-period, two-way crossover, single-dose bioequivalence study in which the active substance ivermectin is administered as a single dose of 12 mg as either CHILD-IVITAB or STROMECTOL during two study drug administration periods. Each treatment will be investigated in the same subgroup of 16 healthy male or female study participants under fasted conditions.
Detailed description
Ivermectin is used in humans as an oral antiparasitic agent. Currently approved ivermectin tablets are designed for adult patients. A child-appropriate formulation is not yet available. Ivermectin in suspension is not practicable as the stability is fragile, the shelf-life is very short, and the suspension is affected by UV light exposure. If tablets are offered to infants and young children as crushed or in a suspended form they are prone to imprecise dosing (loss of product after crushing or sedimentation of product after suspension). They are not palatable, and thereby frequently expelled out of the mouth by the child. All above compromise drug-adherence and effectiveness of treatment. In this bioequivalence study in healthy adults, CHILD-IVITAB, a novel orally disintegrating tablet (ODT) formulation containing the active ingredient ivermectin, will be evaluated. CHILD-IVITABs are stable in hot and humid atmosphere and no external agent is required for taste masking or swallowing. This study aims to determine if 12 mg of CHILD-IVITAB administered in a single dose is bioequivalent (with 0.80, 1.25 as the bioequivalence boundaries for AUC0-∞) to 12 mg administered as a single dose of the reference formulation STROMECTOL under fasting conditions. Further this study aims to characterize tolerability of CHILD-IVITAB in healthy adults.
Interventions
DRUGTreatment A (investigational drug) followed by Treatment B (reference drug)
Two drug administration periods (1 and 2), each consisting of administration of Treatment A (investigational drug) followed by Treatment B (reference drug) on Day 1 will be performed. Post administration of the study drug standard PK sampling, measurement of vital signs, adverse events, ECG and VAS as per schedule will be done over a time period of 11 hours. The study participants will thereafter be discharged. The participants will return to the study center at 24, 48, 72 and 96 hours after study drug administration in each treatment period for blood sampling, vital signs and safety assessments as per schedule. The wash-out period between doses will be at least 7 days.
DRUGTreatment B (reference drug) followed by Treatment A (investigational drug)
Two drug administration periods (1 and 2), each consisting of administration of Treatment B (reference drug) followed by Treatment A (investigational drug) or on Day 1 will be performed. Post administration of the study drug standard PK sampling, measurement of vital signs, adverse events, ECG and VAS as per schedule will be done over a time period of 11 hours. The study participants will thereafter be discharged. The participants will return to the study center at 24, 48, 72 and 96 hours after study drug administration in each treatment period for blood sampling, vital signs and safety assessments as per schedule. The wash-out period between doses will be at least 7 days.
Sponsors
Permamed AG, Switzerland
Galvita AG, Switzerland
University Children's Hospital Basel
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
NONE
Intervention model description
open-label, randomized, two-period, two-way crossover, single-dose bioequivalence study
Eligibility
Sex/Gender
ALL
Age
18 Years to 45 Years
Healthy volunteers
Yes
Inclusion criteria
* Male or female aged between 18 and 45 years (inclusive) at screening. * Healthy adult females on contraceptives at least 1 month prior to the start of the study until 1 month after the completion of the study and urine pregnancy test at screening and pre-study drug administration negative. * No history of alcohol or drug abuse. * No history of chronic liver or kidney disease. * No clinically significant findings on the physical examination at screening. * Body mass index (BMI) between 18.0 and 30.0 kg/m2 (inclusive) at screening. * Normal blood pressure and heart rate (Systolic blood pressure (SBP) 100-145 mmHg, diastolic blood pressure (DBP) 50-90 mmHg, and heart rate (HR) 45-90 bpm (inclusive), measured after 5 minutes in the supine position at screening). * Hematology and blood chemistry results not deviating from the normal range to a clinically relevant extent at screening. Gilbert's syndrome (increased total and unconjugated bilirubin when fasting) will be accepted if mild. * A 12-lead ECG without significant abnormalities (QTc ³450 msec at screening or pronounced sinus bradycardia (\<40 bpm/min), even if elicited by sport) * Negative urine drug screen (amphetamines, benzodiazepines, cannabis, cocaine, and opiates). * Ability to communicate well with the investigator, in the local language, and to understand and comply with the requirements of the study. * The participant agrees to be available for scheduled visits. * Informed and signed consent obtained prior to any study-mandated procedure (including specific request for HIV serology and hepatitis as well as for urinary screen for drugs).
Exclusion criteria
* Eligible participants must meet none of the following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| pharmacokinetics (PK) primary endpoint | At Baseline, at 30 and 60 minutes, at 2, 3, 4, 5, 6, 8, 10, 24, 48, 72 and 96 hours after study drug administration in each treatment period | Change in the area under the plasma concentration-time curve from zero to infinity (AUC0-∞) of ivermectin in each treatment period |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| The area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification (AUC0-tlast) of ivermectin in each treatment period | Over a time period of 11 hours after study drug administration in each treatment period | The area under the plasma concentration-time curve from time zero to time t of the last measured concentration above the limit of quantification (AUC0-tlast) of ivermectin in each treatment period |
| The time to reach maximum plasma concentration (tmax) of ivermectin in each treatment period | Over a time period of 11 hours after study drug administration in each treatment period | The time to reach maximum plasma concentration (tmax) of ivermectin in each treatment period |
| Supine blood pressure (systolic and diastolic) | At Baseline, at 2, 4, 24, 48, 72 and 96 hours after study drug administration in each treatment period and at Day 7-10 of period 2 | Change from baseline to each time point of measurement during each treatment period as per study schedule for supine blood pressure |
| ECG (conduction changes) | At Baseline, at 2, 4 hours after study drug administration in each treatment period and at Day 7-10 of period 2 | Change from baseline to each time point of measurement during each treatment period as per study schedule for ECG variables (conduction system) |
| The maximum plasma concentration (Cmax) of ivermectin in each treatment period | Over a time period of 11 hours after study drug administration in each treatment period | The maximum plasma concentration (Cmax) of ivermectin in each treatment period |
| Tolerability of Treatments A and B utilizing a visual analogue scale (VAS) for gastrointestinal tract (GIT) (2 items) | At Baseline, at 30 and 60 minutes, at 2, 3, 4, 6, 10 hours after study drug administration in each treatment period | Tolerability of Treatments A and B utilizing a VAS for GIT (2 items) ; (0 = tolerable; 10 = very untolerable) |
| Tolerability of Treatments A and B utilizing a VAS for central nervous system (CNS) (6 items) | At Baseline, at 30 and 60 minutes, at 2, 3, 4, 6, 10 hours after study drug administration in each treatment period | Tolerability of Treatments A and B utilizing a VAS for CNS (6 items); (0 = tolerable; 10 = very untolerable) |
| Palatability of Treatments A and B utilizing a VAS (bitterness, sweetness, intensity, and palatability/acceptability) | At 0 and at 30 minutes after study drug administration in each treatment period | Palatability of Treatments A and B utilizing a VAS (bitterness, sweetness, intensity, and palatability/acceptability); (0 = pleasant; 10 = very unpleasant) |
| Heart rate | At Baseline, at 2, 4, 24, 48, 72 and 96 hours after study drug administration in each treatment period and at Day 7-10 of period 2 | Change from baseline to each time point of measurement during each treatment period as per study schedule for Heart rate |
| Adverse events (AEs) reporting from first drug administration up to end of study (EOS) (number of AEs) | From Baseline until Day 7-10 of period 2 (between 4 to a maximum of 7 weeks) | Adverse events (AEs) reporting from first drug administration up to EOS |
Countries
Switzerland
Outcome results
None listed