Trial Outcomes & Findings for Study to Evaluate the PK of PO Omadacycline in Adults With Community-Acquired Bacterial Pneumonia (NCT NCT04160260)

Results Overview

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.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

18 participants

Primary outcome timeframe

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

Results posted on

2021-11-03

Participant Flow

A total of 20 participants were screened. Of these, 2 participants failed screening, and 18 participants were enrolled in the study.

Participant milestones

Participant milestones
Measure	300 mg PO Omadacycline Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Overall Study STARTED	18
Overall Study COMPLETED	18
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Study to Evaluate the PK of PO Omadacycline in Adults With Community-Acquired Bacterial Pneumonia

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	300 mg PO Omadacycline n=18 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Age, Continuous	60.7 Years STANDARD_DEVIATION 11.81 • n=5 Participants
Sex: Female, Male Female	10 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	18 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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

Population: Pharmacokinetic (PK) Population: All participants who received omadacycline and had at least 1 evaluable PK parameter. Two participants who reported emesis within 4 hours post-dose and 1 participant with only Day 1 PK profile and no sampling on Day 2, were excluded from the analysis in 300 mg omadacycline treatment arm. Two additional participants with unusually low PK concentrations deemed as outliers were excluded from the analysis.

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.

Outcome measures

Outcome measures
Measure	300 mg PO Omadacycline n=13 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
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	9.93 Hours x nanograms/milliliter (h*ng/mL) Standard Deviation 0.364

PRIMARY outcome

Timeframe: 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

Population: PK population. Two participants who reported emesis within 4 hours post-dose on Day 1 were excluded from the analysis in 300 mg omadacycline treatment arm. Two additional participants with unusually low PK concentrations deemed as outliers were excluded from the analysis.

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.

Outcome measures

Outcome measures
Measure	300 mg PO Omadacycline n=14 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Log Geometric Mean AUC From Time 0 to 24 Hours After Dosing (AUC[0-24]) of Oral Omadacycline on Day 1	9.27 h*ng/mL Standard Deviation 0.502

PRIMARY outcome

Timeframe: 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

Population: PK population. Two participants who reported emesis within 4 hours post-dose were excluded from the analysis. Additionally, 1 participant with only Day 1 PK profile and no sampling on Day 2, was excluded from the Day 2 analysis.

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.

Outcome measures

Outcome measures
Measure	300 mg PO Omadacycline n=18 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Geometric Mean AUC From Time 0 to the Last Quantifiable Concentration (AUClast) of Oral Omadacycline on Day 1 and Day 2 Day 1	8468.9 h*ng/mL Geometric Coefficient of Variation 89.9
Geometric Mean AUC From Time 0 to the Last Quantifiable Concentration (AUClast) of Oral Omadacycline on Day 1 and Day 2 Day 2	8467.8 h*ng/mL Geometric Coefficient of Variation 69.9

PRIMARY outcome

Timeframe: 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

Population: PK population. Two participants who reported emesis within 4 hours post-dose were excluded from the Day 1 analysis. Additionally, 1 participant with only Day 1 PK profile and no sampling on Day 2, was excluded from the Day 2 analysis.

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.

Outcome measures

Outcome measures
Measure	300 mg PO Omadacycline n=18 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Oral Omadacycline on Day 1 and Day 2 Day 1	721.2 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 83.9
Geometric Mean of Maximum Observed Plasma Concentration (Cmax) of Oral Omadacycline on Day 1 and Day 2 Day 2	708.6 Nanograms per milliliter (ng/mL) Geometric Coefficient of Variation 68.7

PRIMARY outcome

Timeframe: 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

Population: PK population. Two participants who reported emesis within 4 hours post-dose were excluded from the Day 1 analysis. Additionally, 1 participant with only Day 1 PK profile and no sampling on Day 2, was excluded from the Day 2 analysis.

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.

Outcome measures

Outcome measures
Measure	300 mg PO Omadacycline n=18 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Median Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Oral Omadacycline on Day 1 and Day 2 Day 1	3.0 Hours Interval 1.0 to 24.0
Median Time to Reach the Maximum Observed Plasma Concentration (Tmax) of Oral Omadacycline on Day 1 and Day 2 Day 2	2.1 Hours Interval 2.0 to 3.0

PRIMARY outcome

Timeframe: 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

Population: PK population. Two participants who reported emesis within 4 hours post-dose were excluded from the Day 1 analysis. Additionally, 1 participant with only Day 1 PK profile and no sampling on Day 2, was excluded from the Day 2 analysis.

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.

Outcome measures

Outcome measures
Measure	300 mg PO Omadacycline n=15 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
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 Day 1	8.0 Hours Interval 6.0 to 16.0
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 Day 2	13.1 Hours Interval 6.0 to 21.0

SECONDARY outcome

Timeframe: From the first dose of study drug up to 37 days

Population: Safety Population: all enrolled participants who received at least one dose of omadacycline during the study

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.

Outcome measures

Outcome measures
Measure	300 mg PO Omadacycline n=18 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Treatment-related TEAE, and Serious Adverse Event (SAE) TEAEs	10 Participants
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Treatment-related TEAE, and Serious Adverse Event (SAE) Treatment-related TEAEs	8 Participants
Number of Participants With Any Treatment-emergent Adverse Event (TEAE), Treatment-related TEAE, and Serious Adverse Event (SAE) SAEs	0 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 37 days

Population: Intent-to-Treat (ITT) Population: All enrolled participants regardless of whether they received the study drug. However, all enrolled participants had received oral omadacycline during this study.

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.

Outcome measures

Outcome measures
Measure	300 mg PO Omadacycline n=18 Participants Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Number of Participants With Clinical Success, Clinical Failure and Indeterminate Clinical Response at the End of Treatment (EOT) as Determined by Investigator Assessment (IGA) Clinical Success	18 Participants
Number of Participants With Clinical Success, Clinical Failure and Indeterminate Clinical Response at the End of Treatment (EOT) as Determined by Investigator Assessment (IGA) Clinical Failure	0 Participants
Number of Participants With Clinical Success, Clinical Failure and Indeterminate Clinical Response at the End of Treatment (EOT) as Determined by Investigator Assessment (IGA) Indeterminate	0 Participants

Adverse Events

300 mg PO Omadacycline

Serious events: 0 serious events

Other events: 10 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	300 mg PO Omadacycline n=18 participants at risk Participants received omadacycline 300 milligrams (mg) per oral (PO) twice daily (BID) on Day 1, followed by omadacycline 300 mg PO once daily (QD) from Day 2 through Day 10.
Gastrointestinal disorders Nausea	33.3% 6/18 • Number of events 7 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Gastrointestinal disorders Vomiting	16.7% 3/18 • Number of events 5 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Gastrointestinal disorders Abdominal pain upper	11.1% 2/18 • Number of events 2 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Gastrointestinal disorders Abdominal pain	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Infections and infestations Bronchitis	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Infections and infestations Influenza	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Infections and infestations Metapneumovirus infection	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Infections and infestations Oral candidiasis	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Investigations Alanine aminotransferase increased	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Investigations Aspartate aminotransferase increased	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Investigations Blood alkaline phosphatase increased	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Nervous system disorders Dizziness	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).
Respiratory, thoracic and mediastinal disorders Chronic obstructive pulmonary disease	5.6% 1/18 • Number of events 1 • From the first dose of study drug up to 37 days Treatment-emergent adverse events (TEAEs), defined as any AEs that newly appeared, increased in frequency, or worsened in severity on or after the initiation of active test article, were reported for the Safety Population (all enrolled participants who received at least one dose of oral omadacycline during the study).

Additional Information

Paratek Medical Information

Paratek Pharmaceuticals, Inc.

Phone: 1-833-727-2835

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The only disclosure restriction on the Principal Investigator is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days from the time submitted to the sponsor for review. The sponsor can request changes to the communication and require the removal of confidential information.
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