Safety, Tolerability And Pharmacokinetics Study Of Single Doses Of PNU-100480 In Healthy Adults

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the safety, tolerability, and pharmacokinetics of PNU-100480 (PF-02341272) after a single dose in healthy adult volunteers.

Official Title
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A Phase 1 Study To Evaluate The Safety, Tolerability, And Pharmacokinetics Of PNU-100480 (PF-02341272) After First Time Administration Of Ascending Oral Doses To Healthy Adult Subjects Under Fed And Fasted Conditions

Conditions
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Tuberculosis

Intervention / Treatment
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* Drug: PNU-100480
* Drug: PNU-100480
* Drug: Placebo
* Drug: PNU-100480
* Drug: PNU-100480
* Drug: Placebo
* Drug: PNU-100480
* Drug: PNU-100480
* Drug: Placebo
* Drug: PNU-100480
* Drug: PNU-100480
* Drug: PNU-100480
* Drug: Placebo
* Drug: PNU-100480
* Drug: PNU-100480
* Drug: PNU-100480
* Drug: Placebo
* Drug: PNU-100480
* Drug: PNU-100480
* Drug: PNU-100480
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy adult volunteers willing and able to be confined to the Clinical Research Unit and comply with study schedule. Women of non-childbearing potential only. Exclusion Criteria: History of hypersensitivity to, or intolerance of, linezolid. Antibiotic treatment within 14 days prior to dosing.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 55 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cohort 1, Sequence 1<br>Period 1- Placebo Period 2- 100 mg Period 3- 300 mg | Drug: PNU-100480<br>* 100 mg oral suspension given once<br>* Other names: Period 2;Drug: PNU-100480<br>* 300 mg oral suspension given once<br>* Other names: Period 3;Drug: Placebo<br>* placebo to match oral suspension given once<br>* Other names: Period 1;|
| Experimental: Cohort 1, Sequence 2<br>Period 1- 35 mg Period 2- Placebo Period 3- 300 mg | Drug: PNU-100480<br>* 300 mg oral suspension given once<br>* Other names: Period 3;Drug: PNU-100480<br>* 35 mg oral suspension given once<br>* Other names: Period 1;Drug: Placebo<br>* placebo to match oral suspension given once<br>* Other names: Period 2;|
| Experimental: Cohort 1, Sequence 3<br>Period 1- 35 mg Period 2- 100 mg Period 3- Placebo | Drug: PNU-100480<br>* 100 mg oral suspension given once<br>* Other names: Period 2;Drug: PNU-100480<br>* 35 mg oral suspension given once<br>* Other names: Period 1;Drug: Placebo<br>* placebo to match oral suspension given once<br>* Other names: Period 3;|
| Experimental: Cohort 2, Sequence 1<br>Period 1- Placebo Period 2- 1000 mg Period 3- 1500 mg Period 4- 600 mg (Fed conditions) | Drug: PNU-100480<br>* 1000 mg oral suspension given once<br>* Other names: Period 2;Drug: PNU-100480<br>* 1500 mg oral suspension given once<br>* Other names: Period 3;Drug: PNU-100480<br>* Fed conditions, 600 mg oral suspension given once<br>* Other names: Period 4 (Fed);Drug: Placebo<br>* placebo to match oral suspension given once<br>* Other names: Period 1;|
| Experimental: Cohort 2, Sequence 2<br>Period 1- 600 mg Period 2- Placebo Period 3- 1500 mg Period 4- 600 mg (Fed conditions) | Drug: PNU-100480<br>* 1500 mg oral suspension given once<br>* Other names: Period 3;Drug: PNU-100480<br>* 600 mg oral suspension given once<br>* Other names: Period 1;Drug: PNU-100480<br>* Fed conditions, 600 mg oral suspension given once<br>* Other names: Period 4 (Fed);Drug: Placebo<br>* placebo to match oral suspension given once<br>* Other names: Period 2;|
| Experimental: Cohort 2, Sequence 3<br>Period 1- 600 mg Period 2- 1000 mg Period 3- Placebo Period 4- 600 mg (Fed conditions) | Drug: PNU-100480<br>* 1000 mg oral suspension given once<br>* Other names: Period 2;Drug: PNU-100480<br>* 600 mg oral suspension given once<br>* Other names: Period 1;Drug: PNU-100480<br>* Fed conditions, 600 mg oral suspension given once<br>* Other names: Period 4 (Fed);Drug: Placebo<br>* placebo to match oral suspension given once<br>* Other names: Period 3;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Evaluation of safety and tolerability of escalating single oral doses of PNU-100480. |  | Daily, Days 1-3 or 4, and 7-14 days after dosing. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Characterize pharmacokinetics of single oral doses PNU-100480. |  | Predose; multiple timepoints postdose on Day 1, and up to 72 hours postdose. | 
| Characterize the effect of food on the pharmacokinetics of a single oral dose of PNU-100480. |  | Predose; multiple timepoints postdose on Day 1, and up to 72 hours postdose. | 
| Characterize the bactericidal activity in blood of orally administered PNU-100480 against intracellular Mycobacterium tuberculosis in relation to blood concentrations of PNU-100480 (and its metabolites) (some periods only) |  | Predose and timpoints up to 24 hours post dose on Day 1 (only in some periods) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Safety tolerability pharmacokinetics PK first in human FIH