A Drug Interaction Study of the Effects of PPI-668 on the Pharmacokinetics of Midazolam and Omeprazole

A Phase 1, Open-Label Study to Evaluate the Potential Effects of PPI-668 on the Pharmacokinetics of Midazolam and Omeprazole, and Potentially Telaprevir, in Healthy Adult Subjects

The primary objectives of the study are to:

• Evaluate the potential effects of PPI-668 at steady state on the pharmacokinetic (PK) profile of midazolam following a single oral dose in human subjects.
• Evaluate the potential effects of PPI-668 at steady state on the PK profile of omeprazole following a single oral dose in human subject

Study Overview

• Status: Completed
• Conditions: Pharmacokinetic Assessments in Healthy Volunteers
• Intervention / Treatment: Drug: Midazolam; Drug: Omeprazole; Drug: PPI-668; Drug: Telaprevir

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Wisconsin
    • West Bend, Wisconsin, United States, 53095
      • Spaulding Clinical Research

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Subject or legally authorized representative signs an Institutional Review Board (IRB)-approved written informed consent and privacy language as per national regulations (e.g., Health Insurance Portability and Accountability Act [HIPAA] authorization for sites in the United States) before any study-related procedures (including withdrawal of prohibited medication, if applicable) are performed
2. Age 18 to 50 years
3. Body mass index (BMI) 18-32 kg/m2
4. Clinical and laboratory findings consistent with good health in the opinion of the investigator

5. Women of non-childbearing potential or men who agree to utilize adequate contraception throughout the study

   1. Women of non-childbearing potential must be one of the following:

      • Postmenopausal (>2 years amenorrhea and postmenopausal status confirmed by follicle-stimulating hormone levels)
      • Surgically sterile (documentation of prior tubal ligation, hysterectomy, or oophorectomy is required)

   2. Male subjects who are not surgically sterile must agree to use one of the following birth control methods if sexually active:

      • Double-barrier contraceptive (e.g., condom plus diaphragm, condom or diaphragm with spermicidal gel/foam)
      • Female partner is at least two years postmenopausal or surgically sterile

Exclusion Criteria:

1. Positive results on any of the following tests at Screening or Day -1:

   urine pregnancy (women only), urine drugs of abuse and alcohol, hepatitis B surface antigen, hepatitis C antibody, and human immunodeficiency virus antibody

2. Concurrent clinically significant medical diagnosis that would potentially interfere with the subject's study compliance or confound the study results
3. Concurrent social conditions (e.g., drug or alcohol abuse, transportation difficulties) that would potentially interfere with the subject's study compliance
4. Clinically significant illness within 30 days preceding entry into the study
5. Participation in an investigational drug study within 30 days or 5 half-lives, whichever is longer, before Screening
6. Use of prescription medications within 14 days before Day 1 and throughout the study. (The use of non-prescription or over-the-counter medications is prohibited within 7 days before Day 1 and throughout the study. This includes all herbal supplements or remedies and vitamins.)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: midazolam; potential effects of PPI-668 on midazolam pharmacokinetics	Drug: Midazolam; Drug: PPI-668
Experimental: omeprazole; potential effects of PPI-668 on omeprazole pharmacokinetics	Drug: Omeprazole; Drug: PPI-668
Experimental: telaprevir; potential effects of PPI-668 on telaprevir pharmacokinetics	Drug: PPI-668; Drug: Telaprevir

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Midazolam area under the plasma concentration-time curve from time 0 to 24 hours after dosing (AUC0-24)	Days 1-6
Midazolam maximum observed plasma concentration (Cmax)	Days 1-6
Omeprazole area under the plasma concentration-time curve from time 0 to 24 hours after dosing (AUC0-24)	Days 1-6
Omeprazole maximum observed plasma concentration (Cmax)	Days 1-6

Secondary Outcome Measures

Outcome Measure	Time Frame
Telaprevir area under the plasma concentration-time curve from time 0 to 24 hours after dosing (AUC0-24)	Days 1-12
Telaprevir maximum observed plasma concentration (Cmax)	Days 1-12

Collaborators and Investigators

• Sponsor: Presidio Pharmaceuticals, Inc.
• Investigators: Principal Investigator: Paul Rice, MD, Spaulding Clinical

Study record dates

Study Major Dates

• Study Start: February 1, 2013
• Primary Completion (Actual): March 1, 2013
• Study Completion (Actual): March 1, 2013

Study Registration Dates

• First Submitted: February 4, 2013
• First Submitted That Met QC Criteria: February 5, 2013
• First Posted (Estimate): February 8, 2013

Study Record Updates

• Last Update Posted (Estimate): March 26, 2013
• Last Update Submitted That Met QC Criteria: March 22, 2013
• Last Verified: March 1, 2013

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Enzyme Inhibitors; Anesthetics, Intravenous; Anesthetics, General; Anesthetics; Gastrointestinal Agents; Tranquilizing Agents; Psychotropic Drugs; Hypnotics and Sedatives; Adjuvants, Anesthesia; Anti-Anxiety Agents; GABA Modulators; GABA Agents; Anti-Ulcer Agents; Proton Pump Inhibitors; Midazolam; Omeprazole
• Other Study ID Numbers: PPI-668-102