Pharmacokinetic and Mosquito-Lethal Effects of Ivermectin (IVM), Primaquine (PQ), Dihydroartemisinin-Piperaquine (DHA-PQP) and Albendazole (ABZ) in Healthy Subjects

NCT02568098 | Completed Phase 1

• 1 other identifier: FTM1501
• Study Type: interventional
• Target: 16
• Locations: 1 country
• Sites: 1

Brief Summary

Primary Objective

• To evaluate the safety and tolerability of co-administered single dose Dihydroartemisinin-Piperaquine (DHA-PQP), Ivermectin (IVM), Primaquine (PQ), and Albendazole (ABZ) in healthy subjects. Secondary Objectives
• To characterize the potential pharmacokinetic interactions between DHA-PQP, IVM, PQ, and ABZ in healthy adult subjects.
• To characterize the pharmacokinetic properties of PQ (and its major metabolite), DHA-PQP, IVM, and ABZ (and its major metabolite) when given alone and in combination.
• To investigate pharmacogenetic polymorphisms affecting drug levels of PQ, DHA-PQP, IVM, ABZ and their metabolites.
• To determine mosquito lethal efficacy of IVM, PQ, ABZ, and DHA-PQP combinations against Anopheles dirus and Anopheles minimus.
• To determine if IVM concentrations in venous blood differs from capillary blood.

Conditions

Drug Combination; Pharmacokinetics; Healthy

Keywords

Drug combination; Ivermectin; Primaquine; Dihydroartemisinin-Piperaquine; Albendazole; Pharmacokinetics; Mosquito-Lethal Effect; Healthy adult subject

Outcome Measures

Primary Outcomes (1)

• Number of Participants with Adverse Events

  Also including abnormal clinical laboratory, vital signs and corrected QT interval (QTc) prolongation for DHA-PQP

  1.5 year

Secondary Outcomes (11)

• Area under the concentration-time curve AUC(0-∞)

  1.5 year

• Area under the concentration-time curve AUC(0-last)

  1.5 year

• Maximal concentration (Cmax)

  1.5 year

• Elimination clearance (CL/F)

  1.5 year

• Terminal elimination half-life (t1/2)

  1.5 year

Study Arms (3)

TMEC-14-022 (OxTREC 39-14)

EXPERIMENTAL

Subjects had previously taken drug CQ and PQ

Drug: IVM, IVM and PQ, IVM and DHA-PQP, IVM and DHA-PQP and PQ; Drug: PQ and DHA-PQP and PQ

TMEC 12-004 (OxTREC 58-11)

EXPERIMENTAL

Subjects had previously taken drug PQ and DHA-PQP

Drug: IVM, IVM and PQ, IVM and DHA-PQP, IVM and DHA-PQP and PQ

New subject

EXPERIMENTAL

Subjects who not previously participated in study "TMEC 12-004 (OxTREC ref. 58-11)" and study "TMEC 14-022 (OxTREC ref. 39-14)".

Drug: IVM, IVM and PQ, IVM and DHA-PQP, IVM and DHA-PQP and PQ; Drug: PQ and DHA-PQP and PQ; Drug: DHA-PQP

Interventions

IVM, IVM and PQ, IVM and DHA-PQP, IVM and DHA-PQP and PQ DRUG

Regimen 1: IVM; Regimen 2: IVM and PQ; Regimen 3: IVM and DHA-PQP; Regimen 4: IVM and DHA-PQP and PQ;

New subject; TMEC 12-004 (OxTREC 58-11); TMEC-14-022 (OxTREC 39-14)

PQ and DHA-PQP and PQ DRUG

Regimen 5: PQ; Regimen 7: DHA-PQP and PQ

New subject; TMEC-14-022 (OxTREC 39-14)

DHA-PQP DRUG

Regimen 6: DHA-PQP

New subject

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Healthy as judged by a responsible physician with no abnormality identified on a medical evaluation including medical history and physical examination.
• Males and Females non-smoker aged between 18 years to 60 years.
• Males and Females weight between 36-75 kilograms.
• A female is eligible to enter and participate in this study if she is:
• of non-childbearing potential including pre-menopausal females with documented (medical report verification) hysterectomy or double oophorectomy
• or postmenopausal defined as 12 months of spontaneous amenorrhea or 6 months of spontaneous amenorrhea with serum follicle stimulating hormone levels \>40 milli-International unit (mIU/mL) or 6 weeks postsurgical bilateral oophorectomy with or without hysterectomy
• or of childbearing potential, has a negative serum pregnancy test at screening and prior to start the study drug in each period, and abstain from sexual intercourse or agrees to using effective contraceptive methods (e.g., intrauterine device, hormonal contraceptive drug, tubal ligation or female barrier method with spermicide) during the study until completion of the follow-up procedures
• A male is eligible to enter and participate in this study if he: agrees to abstain from (or use a condom during) sexual intercourse with females of childbearing potential or lactating females; or is willing to use a condom/spermicide, during the study until completion of the follow-up procedures.
• Provide a signed and dated written informed consent prior to study participation.
• Normal electrocardiogram (ECG) with QTc \<450 msec.
• Willingness and ability to comply with the study protocol for the duration of the trial.

You may not qualify if:

• Females who are pregnant, trying to get pregnant, or are lactating.
• The subject has evidence of active substance abuse that may compromise safety, pharmacokinetics, or ability to adhere with protocol instructions.
• A positive pre-study hepatitis B surface antigen, positive hepatitis C antibody, or positive human immunodeficiency virus-1 (HIV-1) antibody result at screening.
• Subjects with a personal history of cardiac disease, symptomatic or asymptomatic arrhythmias, syncopal episodes, or additional risk factors for torsades de points (heart failure, hypokalemia) or with a family history of sudden cardiac death.
• A creatinine clearance (CLcr) \<70 mL/min as determined by Cockcroft-Gault equation:
• CLcr (mL/min) = (140 - age) \* Wt / (72 \* Scr) (multiply answer by 0.85 for females) Where age is in years, weight (wt) is in kg, and serum creatinine (Scr) is in units of mg/dL \[Cockcroft, 1976\].
• History of alcohol or substance abuse or dependence within 6 months of the study.
• Use of prescription (especially cytochrome P450 3A4 (CYP3A4) inhibitors or inducers) or non-prescription drugs except paracetamol at doses of up to 2 grams/day, including vitamins (especially vitamin C), herbal and dietary supplements (including St. John's Wort) within 7 days (or 14 days if the drug is a potential enzyme inducer) or 5 times the drug half-life (whichever is longer) prior to the first dose of study medication until the completion of the follow-up procedure, unless in the opinion of investigator, the medication will not interfere with the study procedures or compromise subject safety; the investigator will take advice from the manufacturer representative as necessary.
• The subject has participated in a clinical trial and has received a drug or a new chemical entity within 30 days or 5 half-lives, or twice the duration of the biological effect of any drug (whichever is longer) prior to the first dose of study medication.
• The subject is unwilling to abstain from ingesting alcohol within 48 hours prior to the first dose of study medication until collection of the final pharmacokinetic sample during each regimen.
• Subjects who have donated blood to the extent that participation in the study would result in more than 300 mL blood donated within a 30-day period. Plasma donation during the study is not acceptable.
• Subjects who have a history of allergy to the study drug or drugs of this class, or a history of drug or other allergy that, in the opinion of the investigator, contraindicates participation in the trial. In addition, if heparin is used during pharmacokinetic sampling, subjects with a history of sensitivity to heparin or heparin-induced thrombocytopenia should not be enrolled.
• Lack of suitability for participation in this study, including but not limited to, unstable medical conditions, systemic disease manifested by tendency to granulocytopenia e.g. rheumatoid arthritis and lupus erythematosus that in the opinion of the investigator would compromise their participation in the trial.
• Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) \>1.5 upper limit of normal (ULN)
• Subjects with history of renal disease, hepatic disease, and/or cholecystectomy

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol University: collaborator
• Mahidol Oxford Tropical Medicine Research Unit: collaborator

Study Sites (1)

Faculty of Tropical Medicine

Bangkok, 10400, Thailand

Location

MeSH Terms

Interventions

Intravital Microscopy

Intervention Hierarchy (Ancestors)

Microscopy; Diagnostic Imaging; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques

Study Officials

• Dr.Podjanee Jittamala, MD

  Mahidol University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: May 26, 2015
• First Posted: October 5, 2015
• Study Start: October 1, 2015
• Primary Completion: December 1, 2016
• Study Completion: December 1, 2016
• Last Updated: May 31, 2017

Record last verified: 2017-05

Locations

TH (1)