Bioequivalence of a Single-dose of 12 mg IVERMECTIN as Orally Disintegrating Mini Tablets Versus a Single-dose of 12 mg Regular IVERMECTIN Tablets in Healthy Adults Under Fasting Conditions

NCT05477810 | Completed Early Phase 1

• 1 other identifier: 2022-01276; ks21Pfister2
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

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.

Conditions

Bioequivalence

Keywords

CHILD-IVITAB; STROMECTOL; Ivermectin; Palatability

Outcome Measures

Primary Outcomes (1)

• pharmacokinetics (PK) primary endpoint

  Change in the area under the plasma concentration-time curve from zero to infinity (AUC0-∞) of ivermectin in each treatment period

  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

Secondary Outcomes (10)

• 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 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 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

• 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

• 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

Study Arms (2)

Treatment A (CHILD-IVITAB) before Treatment B (STROMECTOL)

EXPERIMENTAL

A single oral dose of 12 mg CHILD-IVITAB administered as four ODTs of 3 mg (given in the fasted state in the morning). A single oral dose of 12 mg STROMECTOL administered as four tablets of 3 mg (given in the fasted state in the morning). The wash-out period between doses will be at least 7 days.

Drug: Treatment A (investigational drug) followed by Treatment B (reference drug); Drug: Treatment B (reference drug) followed by Treatment A (investigational drug)

Treatment B (STROMECTOL) before Treatment A (CHILD-IVITAB)

ACTIVE COMPARATOR

A single oral dose of 12 mg STROMECTOL administered as four tablets of 3 mg (given in the fasted state in the morning). A single oral dose of 12 mg CHILD-IVITAB administered as four ODTs of 3 mg (given in the fasted state in the morning). The wash-out period between doses will be at least 7 days.

Drug: Treatment A (investigational drug) followed by Treatment B (reference drug); Drug: Treatment B (reference drug) followed by Treatment A (investigational drug)

Interventions

Treatment A (investigational drug) followed by Treatment B (reference drug) 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.

Treatment A (CHILD-IVITAB) before Treatment B (STROMECTOL); Treatment B (STROMECTOL) before Treatment A (CHILD-IVITAB)

Treatment B (reference drug) followed by Treatment A (investigational drug) 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.

Treatment A (CHILD-IVITAB) before Treatment B (STROMECTOL); Treatment B (STROMECTOL) before Treatment A (CHILD-IVITAB)

Eligibility Criteria

• Age: 18 Years - 45 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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).

You may not qualify if:

• Known hypersensitivity to any excipients of the drug formulations.
• Treatment with another investigational drug within 3 months prior to screening.
• Participation in a clinical study/trial in the previous 3 months unless no treatment taken or large amounts of blood collected
• History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening.
• Significant caffeine consumption defined as \> 400 mg per day at screening.
• History or clinical evidence of any disease and/or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drug.
• History of moderate or severe allergy or asthma at any time. Allergic rhinitis is acceptable if non symptomatic when starting the study and if symptoms are not anticipated to occur during the first 4 weeks of each period and are not expected to require a corticosteroid treatment.
• History of cardiovascular dysfunction if considered as clinically relevant (conduction abnormality, arrhythmia, bradycardia, angina pectoris, cardiac hypertrophy unless elicited by training, embolism).
• Recurrent hypotensive events considered as clinically relevant.
• Use of any medication the week prior to study or as based on 5 plasma half-life rule (before screening, after screening) and throughout study. Paracetamol is permissible before the study as a rescue medication but only with investigator's permission.
• Smoking (consumption of ≤5 cigarettes/day or equivalent is acceptable, provided the subject commits to quit entirely during the study)
• Loss of 350 ml or more of blood or blood donation within 3 months prior to screening.
• Positive results from the hepatitis serology, except for vaccinated (hepatitis B virus) participants, at screening.
• Positive results from the HIV serology at screening.
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Sponsors & Collaborators

• University Children's Hospital Basel: lead
• Permamed AG, Switzerland: collaborator
• Galvita AG, Switzerland: collaborator

Study Sites (1)

University Hospital CHUV, Service of Clinical Pharmacology

Lausanne, 1011, Switzerland

Location

MeSH Terms

Interventions

Drugs, Investigational

Intervention Hierarchy (Ancestors)

Pharmaceutical Preparations

Study Officials

• Marc Pfister, Prof. Dr. med.

  Universitäts-Kinderspital beider Basel (UKBB)

  STUDY DIRECTOR

• Laura Rothuizen, Dr. med.

  University Hospital CHUV, Service of Clinical Pharmacology

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: OTHER
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: open-label, randomized, two-period, two-way crossover, single-dose bioequivalence study

Study Record Dates

• First Submitted: July 20, 2022
• First Posted: July 28, 2022
• Study Start: September 13, 2022
• Primary Completion: December 15, 2022
• Study Completion: December 15, 2022
• Last Updated: December 22, 2022

Record last verified: 2022-12

Locations

CH (1)