Study to Evaluate the PK of PO Omadacycline in Adults With Community-Acquired Bacterial Pneumonia
Primary Purpose
Community-acquired Pneumonia
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Omadacycline
Sponsored by
About this trial
This is an interventional treatment trial for Community-acquired Pneumonia
Eligibility Criteria
Inclusion Criteria:
- Male or female participants, age 18 or older who have signed the informed consent form
- Must have a qualifying community-acquired bacterial pneumonia
- Has disease severity such that oral antibiotics therapy is appropriate
- Participants must not be pregnant at the time of enrollment
- Must agree to a reliable method of birth control during the study and for 30 days following the last dose of study drug
- Must be able to swallow tablets and comply with all of the requirements of the study
Exclusion Criteria:
- Has received more than 24 hours of a potentially effective systemic antibacterial therapy within the 72 hours prior to the first dose of test article
- Known or suspected infection caused by a pathogen that may be resistant to test article
- Participants who reside in a long-term care or nursing home
- Evidence of empyema
- Evidence of significant immunological disease
- Evidence of liver impairment or disease
- Evidence of unstable cardiac disease
- Severe renal disease or requirement for dialysis
- Evidence of septic shock
- Has a history of hypersensitivity or allergic reaction to any tetracycline
- Has received an investigational drug within the past 30 days
- Participants who are pregnant or nursing
- Unable or unwilling to comply with the protocol requirements
Sites / Locations
- Site 105
- Site 102
- Site 104
- Site 111
- Site 116
- Site 106
- Site 108
- Site 110
- Site 112
- Site 103
- Site 114
- Site 101
- Site 109
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Omadacycline: Omadacycline Tablets
Arm Description
Outcomes
Primary Outcome Measures
Log Geometric Mean Area Under the Concentration Versus Time Curve (AUC) From Time 0 to 48 Hours After Dosing (AUC[0-48]) of Oral Omadacycline on Day 2
AUC(0-48) was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated statistical analysis software (SAS) program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this pharmacokinetic (PK) endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis. Data for 100 mg intravenous (IV) omadacycline treatment group which was used for comparison in the statistical analysis were obtained from 6 completed studies: PTK 0796-SDES-0501, PTK 0796-BEQU-0801, PTK 0796 WOIV-0703, CPTK796-A2104, CPTK796-A2201, and PTK 0796-RENL-15102. NCT numbers of these studies were not available.
Log Geometric Mean AUC From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Oral Omadacycline on Day 1
AUC(0-24) was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated SAS program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Day 1, the participant was excluded from PK Analysis. Data for 100 mg intravenous (IV) omadacycline treatment group which was used for comparison in the statistical analysis were obtained from 6 completed studies: PTK 0796-SDES-0501, PTK 0796-BEQU-0801, PTK 0796 WOIV-0703, CPTK796-A2104, CPTK796-A2201, and PTK 0796-RENL-15102. NCT numbers of these studies were not available.
Geometric Mean AUC From Time 0 to the Last Quantifiable Concentration (AUClast) of Oral Omadacycline on Day 1 and Day 2
AUClast was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated SAS program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis.
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Oral Omadacycline on Day 1 and Day 2
Cmax was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated SAS program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis.
Median Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Oral Omadacycline on Day 1 and Day 2
Tmax was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated SAS program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis.
Median Elimination Half-life Associated With the Terminal Slope of the Semilogarithmic Concentration-time Curve (T1/2) of Oral Omadacycline on Day 1 and Day 2
T1/2 was calculated using the linear regression of the terminal portion of the natural log-plasma concentration versus time curve. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis.
Secondary Outcome Measures
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Treatment-related TEAE, and Serious Adverse Event (SAE)
AEs were defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as AEs that began (or pre-existing AEs that worsened) on or after the first dose. SAEs were defined as any untoward medical occurrence that, at any dose resulted in: death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention.
Full Information
NCT ID
NCT04160260
First Posted
November 8, 2019
Last Updated
October 5, 2021
Sponsor
Paratek Pharmaceuticals Inc
1. Study Identification
Unique Protocol Identification Number
NCT04160260
Brief Title
Study to Evaluate the PK of PO Omadacycline in Adults With Community-Acquired Bacterial Pneumonia
Official Title
A Phase 1 Multi-Center Study to Measure the Pharmacokinetics of Oral Omadacycline in Adult Subjects With Community-Acquired Bacterial Pneumonia (CABP)
Study Type
Interventional
2. Study Status
Record Verification Date
October 2021
Overall Recruitment Status
Completed
Study Start Date
November 28, 2019 (Actual)
Primary Completion Date
March 23, 2020 (Actual)
Study Completion Date
April 13, 2020 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Paratek Pharmaceuticals Inc
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
The purpose of this study is to evaluate the pharmacokinetics of an oral omadacycline dosing regimen in the treatment of adults with CABP.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Community-acquired Pneumonia
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
18 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Omadacycline: Omadacycline Tablets
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Omadacycline
Other Intervention Name(s)
NUZRYA
Intervention Description
Omadacycline: PO Tablets
Primary Outcome Measure Information:
Title
Log Geometric Mean Area Under the Concentration Versus Time Curve (AUC) From Time 0 to 48 Hours After Dosing (AUC[0-48]) of Oral Omadacycline on Day 2
Description
AUC(0-48) was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated statistical analysis software (SAS) program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this pharmacokinetic (PK) endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis. Data for 100 mg intravenous (IV) omadacycline treatment group which was used for comparison in the statistical analysis were obtained from 6 completed studies: PTK 0796-SDES-0501, PTK 0796-BEQU-0801, PTK 0796 WOIV-0703, CPTK796-A2104, CPTK796-A2201, and PTK 0796-RENL-15102. NCT numbers of these studies were not available.
Time Frame
Day 1: pre-dose; 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 13, 13.5, 14, 14.5, 15, 16, and 24 hours post dose. Day 2: pre-dose; 1, 1.5, 2, 2.5, 3, 4, and 6 hours post dose
Title
Log Geometric Mean AUC From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Oral Omadacycline on Day 1
Description
AUC(0-24) was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated SAS program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Day 1, the participant was excluded from PK Analysis. Data for 100 mg intravenous (IV) omadacycline treatment group which was used for comparison in the statistical analysis were obtained from 6 completed studies: PTK 0796-SDES-0501, PTK 0796-BEQU-0801, PTK 0796 WOIV-0703, CPTK796-A2104, CPTK796-A2201, and PTK 0796-RENL-15102. NCT numbers of these studies were not available.
Time Frame
Day 1: pre-dose; 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 13, 13.5, 14, 14.5, 15, 16, and 24 hours post dose
Title
Geometric Mean AUC From Time 0 to the Last Quantifiable Concentration (AUClast) of Oral Omadacycline on Day 1 and Day 2
Description
AUClast was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated SAS program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis.
Time Frame
Day 1: pre-dose; 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 13, 13.5,14, 14.5, 15, 16, and 24 hours post dose; Day 2: pre-dose; 1, 1.5, 2,2.5, 3, 4, and 6 hours post dose
Title
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Oral Omadacycline on Day 1 and Day 2
Description
Cmax was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated SAS program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis.
Time Frame
Day 1: pre-dose; 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 13, 13.5,14, 14.5, 15, 16, and 24 hours post dose; Day 2: pre-dose; 1, 1.5, 2,2.5, 3, 4, and 6 hours post dose
Title
Median Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Oral Omadacycline on Day 1 and Day 2
Description
Tmax was calculated using the linear trapezoidal linear interpolation method using WinNonlin validated SAS program. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis.
Time Frame
Day 1: Pre-dose, 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 13, 13.5,14, 14.5, 15, 16, 24 hours post dose; Day 2: Pre-dose, 1, 1.5, 2,2.5, 3, 4, 6 hours post-dose
Title
Median Elimination Half-life Associated With the Terminal Slope of the Semilogarithmic Concentration-time Curve (T1/2) of Oral Omadacycline on Day 1 and Day 2
Description
T1/2 was calculated using the linear regression of the terminal portion of the natural log-plasma concentration versus time curve. Participants with plasma concentration data above the limit of quantification were included in the analysis for this PK endpoint. If any participant had an emesis within 4 hours after dosing on Study Days 1 and 2, the participant was excluded from PK Analysis.
Time Frame
Day 1: pre-dose; 1, 1.5, 2, 2.5, 3, 4, 6, 8, 12, 13, 13.5,14, 14.5, 15, 16, and 24 hours post dose; Day 2: pre-dose; 1, 1.5, 2,2.5, 3, 4, and 6 hours post dose
Secondary Outcome Measure Information:
Title
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Treatment-related TEAE, and Serious Adverse Event (SAE)
Description
AEs were defined as any untoward medical occurrence in a participant or clinical investigation participant, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. TEAEs were defined as AEs that began (or pre-existing AEs that worsened) on or after the first dose. SAEs were defined as any untoward medical occurrence that, at any dose resulted in: death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity, was a congenital anomaly/birth defect, or was an important medical event that may have jeopardized the participant or may have required medical or surgical intervention.
Time Frame
From the first dose of study drug up to 37 days
Other Pre-specified Outcome Measures:
Title
Number of Participants With Clinical Success, Clinical Failure and Indeterminate Clinical Response at the End of Treatment (EOT) as Determined by Investigator Assessment (IGA)
Description
The investigator determined whether or not the participant met the criteria of 1 of the following clinical outcomes: Clinical success, clinical failure, and indeterminate. Clinical success: Participant was alive and the infection was sufficiently resolved such that further antibacterial therapy was not needed. Clinical Failure: Participant required alternative antibacterial treatment for community-acquired bacterial pneumonia (CABP) prior to EOT related to either progression or development of new symptoms of CABP or development of infectious complications of CABP (eg, empyema, lung abscess) or participant developed an AE that required discontinuation of study therapy. Indeterminate: the clinical response to test article could not be adequately inferred.
Time Frame
Up to 37 days
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Male or female participants, age 18 or older who have signed the informed consent form
Must have a qualifying community-acquired bacterial pneumonia
Has disease severity such that oral antibiotics therapy is appropriate
Participants must not be pregnant at the time of enrollment
Must agree to a reliable method of birth control during the study and for 30 days following the last dose of study drug
Must be able to swallow tablets and comply with all of the requirements of the study
Exclusion Criteria:
Has received more than 24 hours of a potentially effective systemic antibacterial therapy within the 72 hours prior to the first dose of test article
Known or suspected infection caused by a pathogen that may be resistant to test article
Participants who reside in a long-term care or nursing home
Evidence of empyema
Evidence of significant immunological disease
Evidence of liver impairment or disease
Evidence of unstable cardiac disease
Severe renal disease or requirement for dialysis
Evidence of septic shock
Has a history of hypersensitivity or allergic reaction to any tetracycline
Has received an investigational drug within the past 30 days
Participants who are pregnant or nursing
Unable or unwilling to comply with the protocol requirements
Facility Information:
Facility Name
Site 105
City
Birmingham
State/Province
Alabama
ZIP/Postal Code
35215
Country
United States
Facility Name
Site 102
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Site 104
City
San Diego
State/Province
California
ZIP/Postal Code
92123
Country
United States
Facility Name
Site 111
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
Site 116
City
Clearwater
State/Province
Florida
ZIP/Postal Code
33756
Country
United States
Facility Name
Site 106
City
Doral
State/Province
Florida
ZIP/Postal Code
33166
Country
United States
Facility Name
Site 108
City
Miami
State/Province
Florida
ZIP/Postal Code
33155
Country
United States
Facility Name
Site 110
City
Miami
State/Province
Florida
ZIP/Postal Code
33165
Country
United States
Facility Name
Site 112
City
West Palm Beach
State/Province
Florida
ZIP/Postal Code
33409
Country
United States
Facility Name
Site 103
City
Butte
State/Province
Montana
ZIP/Postal Code
59701
Country
United States
Facility Name
Site 114
City
Las Vegas
State/Province
Nevada
ZIP/Postal Code
89106
Country
United States
Facility Name
Site 101
City
Sherman
State/Province
Texas
ZIP/Postal Code
75092
Country
United States
Facility Name
Site 109
City
Madison
State/Province
Wisconsin
ZIP/Postal Code
53717
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Study to Evaluate the PK of PO Omadacycline in Adults With Community-Acquired Bacterial Pneumonia
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