Drug-drug Interaction Study Between Lopinavir/Ritonavir and Isavuconazole

NCT01660477 | Completed Phase 1

• 1 other identifier: 9766-CL-0035
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this two part study is to assess the effect of multiple doses of isavuconazole on the pharmacokinetics of multiple doses of lopinavir/ritonavir and the effect of multiple doses of lopinavir/ritonavir on the pharmacokinetics of isavuconazole. Part 1 of the study includes 12 subjects randomized to receive either isavuconazole alone or isavuconazole in combination with lopinavir/ritonavir. The purpose of Part 1 is to evaluate safety and tolerability and to establish the effect of multiple doses of lopinavir/ritonavir on isavuconazole. Part 2, if initiated, includes 54 subjects randomized to receive isavuconazole alone, lopinavir/ritonavir alone, or isavuconazole in combination with lopinavir/ritonavir.

Conditions

Pharmacokinetics of Isavuconazole; Pharmacokinetics of Lopinavir/Ritonavir; Healthy Volunteers

Keywords

Isavuconazole; Lopinavir/ritonavir; Healthy Volunteers; BAL8557; Kaletra ®

Outcome Measures

Primary Outcomes (3)

• Pharmacokinetic (PK) for isavuconazole: AUCtau

  (Arms 1 and 3) Area under the concentration time curve during the during time interval between consecutive dosing (AUCtau) (tau=24)

  Part 1, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8,10,12,16, and 24 hours post-dose

• Pharmacokinetic (PK) profile for isavuconazole: AUC tau and Cmax

  (Arms 2 and 3) Maximum concentration (Cmax)

  Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 16, 24 hours post dose

• Pharmacokinetic (PK) profile for lopinavir/ritonavir: AUC tau and Cmax

  (Arms 2 and 3) AUC during time interval between consecutive dosing (AUCtau) (tau=12)

  Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, and 12 hours post dose

Secondary Outcomes (5)

• PK for isavuconazole (in plasma): trough concentration (Ctrough)

  Parts 1 and 2, Days 3, 5, 7, 9 and 11: pre-dose

• PK profile for isavuconazole (in plasma): Cmax, tmax

  Parts 1 and 2, Day 13: predose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12,16, and 24 hours post-dose

• PK for lopinavir/ritonavir (in plasma): trough concentration (Ctrough)

  Part 2, Days 3, 5, 7, 9 and 11: pre-dose

• PK for lopinavir/ritonavir (in plasma): tmax

  Part 2, Day 13: pre-dose, 0.5, 1, 2, 3, 4, 6, 8, 10, 12 hours post dose

• Safety and tolerability of isavuconazole alone and in combination with lopinavir (LPV) and ritonavir (RTV) assessed by recording of adverse events, physical examination, clinical laboratory evaluation, electrocardiograms (ECGs) and vital signs

  Part 1, Days 1 - 20 ± 2

Study Arms (3)

Arm 1: isavuconazole only

EXPERIMENTAL

Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13

Drug: Isavuconazole

Arm 2 : LPV/RTV only

EXPERIMENTAL

Lopinavir/ritonavir (LPV/RTV) twice daily (BID) on Days 1-12 and once on Day 13

Drug: Lopinavir/ritonavir

Arm 3: isavuconazole and LPV/RTV

EXPERIMENTAL

Isavuconazole three times per day (TID) on Days 1-2, and once daily (QD) on Days 3 thru 13 in combination with lopinavir/ritonavir twice daily (BID) on Days 1-13

Drug: Isavuconazole; Drug: Lopinavir/ritonavir

Interventions

Isavuconazole DRUG

oral

Also known as: BAL8557

Arm 1: isavuconazole only; Arm 3: isavuconazole and LPV/RTV

Lopinavir/ritonavir DRUG

oral

Also known as: KALETRA®

Arm 2 : LPV/RTV only; Arm 3: isavuconazole and LPV/RTV

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• The subject has a body weight of at least 45 kg and has a body mass index (BMI) of 18 to 32 kg/m2, inclusive
• Results for aspartate aminotransferase (AST) and alanine aminotransferase (ALT), total bilirubin, lipase, amylase, glucose and triglycerides must be within the normal range
• The female subject agrees to sexual abstinence, or is surgically sterile, postmenopausal (defined as at least 2 years at Screening without menses), or using a medically acceptable double barrier method (e.g. spermicide and diaphragm, or spermicide and condom) to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study; and is not lactating or pregnant as documented by negative pregnancy tests at Screening and Day -1
• The male subject agrees to sexual abstinence, is surgically sterile, or is using a medically acceptable method to prevent pregnancy and agrees to continue using this method from Screening until 3 weeks after the follow-up visit at the end of the study

You may not qualify if:

• The subject has a history of unexplained syncope, cardiac arrest, unexplained cardiac arrhythmia or torsade de pointes, structural heart disease, or family history of Long QT syndrome (suggested by sudden death of a close relative at a young age due to possible or probable cardiac causes)
• The subject has a history of pancreatitis
• The subject has a positive result for hepatitis C antibodies, hepatitis B surface antigen at Screening or is known to be positive for human immunodeficiency virus (HIV)
• The subject has a known or suspected allergy to any of the components of the trial products including lopinavir/ritonavir or the azole class of compounds, or a history of multiple and/or severe allergies to drugs or foods (as judged by the investigator), or a history of severe anaphylactic reactions- - The subject is a smoker (any use of tobacco or nicotine containing products) within 6 months prior to Screening
• The subject has had treatment with prescription drugs or complementary and alternative medicines within 14 days prior to Day -1, or over-the-counter medications within 1 week prior to Day -1, with the exception of acetaminophen up to 2 g/day
• The subject has a recent history (within the last 2 years) of drug or alcohol abuse, as defined by the investigator, or a positive drug and/or alcohol screen
• The subject has participated in a previous isavuconazole study

Sponsors & Collaborators

• Astellas Pharma Global Development, Inc.: lead
• Basilea Pharmaceutica International Ltd: collaborator

Study Sites (1)

Parexel International

Glendale, California, 91206, United States

Location

MeSH Terms

Interventions

isavuconazole; Lopinavir; lopinavir-ritonavir drug combination

Intervention Hierarchy (Ancestors)

Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Medical Director

  Astellas Pharma Global Development

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 6, 2012
• First Posted: August 8, 2012
• Study Start: June 1, 2012
• Primary Completion: October 1, 2012
• Study Completion: October 1, 2012
• Last Updated: February 23, 2015

Record last verified: 2015-02

Locations

US (1)