IV or IV/PO Omadacycline vs. IV/PO Levofloxacin for the Treatment of Acute Pyelonephritis

NCT03757234 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: PTK0796-AP-17202
• Study Type: interventional
• Target: 201
• Locations: 4 countries
• Sites: 31

Brief Summary

The purpose of this study was to evaluate the safety and efficacy of intravenous (iv) or iv/per oral (po) omadacycline as compared to iv or iv/po levofloxacin in the treatment of female adults with acute pyelonephritis.

Conditions

Acute Pyelonephritis

Outcome Measures

Primary Outcomes (4)

• Number of Participants With an Investigator Assessment of Clinical Response at the Post Therapy Evaluation (PTE) Visit (ITT Population)

  Clinical response was determined by the investigator at the PTE visit by assessing whether or not the participant met the clinical outcome of Clinical Success, Clinical Failure, or Indeterminate. Clinical Success was defined as the complete resolution or significant improvement of the baseline AP signs and symptoms at the PTE visit such that no additional antimicrobial therapy is required for the current infection. Clinical Failure was defined as no apparent response to therapy or persistence of signs and symptoms of infection or reappearance of signs and symptoms at or before the PTE visit such that use of additional systemic antimicrobial therapy for the current infection was required or death at or before the PTE visit. The clinical outcome was deemed as Indeterminate when the PTE visit was not completed.

  Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

• Number of Participants With a Microbiological Response at the PTE Visit (Micro-ITT Population)

  Microbiological response was determined programmatically at the PTE visit by assessing whether or not the participant met the microbiological outcome of 'Success', 'Failure', or 'Indeterminate'. Participants were considered to have a microbiological response of 'Success' if the outcomes of each baseline pathogens were eradication at the PTE visit. Participants were considered to have a microbiological response of 'Failure' if the outcome for any pathogen was persistence. Participants were considered to have a microbiological response of 'Indeterminate', if the outcome of at least 1 baseline pathogen was indeterminate and there was no outcome of persistence for any baseline pathogen.

  Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

• Number of Participants With Resolution of All AP Signs and Clinical Symptoms at PTE Visit (ITT Population)

  Participants recorded their assessments using the Modified Patient Symptom Assessment Questionnaire (mPSAQ), a 6-item questionnaire that assessed the levels of 'severity' and 'bothersomeness' for six pyelonephritis signs and symptoms. The sub-scale responses were recorded as 'did not have', 'mild', 'moderate', and 'severe' for 'severity'; and 'not at all', 'a little', 'moderately', and 'a lot' for 'bothersomeness', both scored 0-3. Total scores were calculated by summing the non-missing scores of the 6 items, divided by the number of non-missing items, and then multiplied by 6. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 18 (worst severity/most bothersome). Number of participants with resolution of all symptoms, without occurrence of new symptoms is reported. Resolution was defined as absence of all baseline symptoms.

  Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

• Number of Participants With No Worsening and Absence of New AP Signs and Clinical Symptoms at PTE Visit (ITT Population)

  Participants recorded their assessments using the mPSAQ, a 6-item questionnaire that assessed the levels of 'severity' and 'bothersomeness' for six pyelonephritis signs and symptoms. The sub-scale responses were recorded as 'did not have', 'mild', 'moderate', and 'severe' for 'severity'; and 'not at all', 'a little', 'moderately', and 'a lot' for 'bothersomeness', both scored 0-3. Total scores were calculated by summing the non-missing scores of the 6 items, divided by the number of non-missing items, and then multiplied by 6. For each sub-scale, the total score ranged from 0 (least Severe/ least bothersome) and 18 (worst severity/most bothersome). Number of participants with no worsening and absence of AP signs and clinical symptoms is reported. No worsening meant that each question score is same or better at post baseline.

  Day 21 (A PTE occurred on Day 21 ± 2 days after the participant's first dose of study drug).

Secondary Outcomes (1)

• Number of Participants With Treatment Emergent Adverse Events and Serious Adverse Events

  up to approximately 28 days

Study Arms (5)

Omadacycline 200 iv/200 iv

EXPERIMENTAL

On Day 1, participants received omadacycline 200 milligrams intravenously (iv). On Days 2 through 7, participants continued to receive omadacycline 200 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.

Drug: Omadacycline

Omadacycline 200 iv/100 iv

EXPERIMENTAL

On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes.

Drug: Omadacycline

Omadacycline 200 iv/300 po or 100 iv

EXPERIMENTAL

On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 300 milligrams per oral (po). All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

Drug: Omadacycline

Omadacycline 200 iv/450 po or 100 iv

EXPERIMENTAL

On Day 1, participants received omadacycline 200 milligrams iv. On Days 2 through 7, participants received omadacycline 100 milligrams iv or omadacycline 450 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

Drug: Omadacycline

Levofloxacin 750 iv/750 po or iv

ACTIVE COMPARATOR

On Day 1, participants received levofloxacin 750 milligrams iv. On Days 2 through 7, participants received levofloxacin 750 milligrams iv or levofloxacin 750 milligrams po. All doses were administered once-per-day and iv doses were administered in 150 milliliters of normal saline as continuous infusions over 90 minutes. All oral doses were taken in a fasted state.

Drug: Levofloxacin

Interventions

Omadacycline DRUG

po tablets

Also known as: Nuzyra

Omadacycline 200 iv/300 po or 100 iv; Omadacycline 200 iv/450 po or 100 iv

Levofloxacin DRUG

iv solution/po tablets

Also known as: Levaquin

Levofloxacin 750 iv/750 po or iv

Eligibility Criteria

• Age: 18 Years - 65 Years
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Female participants, age 18-65 years who have signed the informed consent form
• Must have a qualifying acute pyelonephritis
• 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 comply with all of the requirements of the study

You may not qualify if:

• Males
• Symptoms of acute pyelonephritis present for longer 7 days prior to randomization
• Infections that require antibacterial treatment for greater than 14 days
• Evidence of suspected non-renal source of infections, vaginitis, or sexually transmitted infection
• 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 or to levofloxacin
• 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

Sponsors & Collaborators

• Paratek Pharmaceuticals Inc: lead

Study Sites (31)

Site 201

Tbilisi, Georgia

Location

Site 202

Tbilisi, Georgia

Location

Site 203

Tbilisi, Georgia

Location

Site 204

Tbilisi, Georgia

Location

Site 301

Daugavpils, Latvia

Location

Site 304

Liepāja, LV-3414, Latvia

Location

Site 305

Rēzekne, Latvia

Location

Site 302

Riga, Latvia

Location

Site 303

Valmiera, Latvia

Location

Site 409

Krasnoyarsk, 660062, Russia

Location

Site 408

Moscow, 141435, Russia

Location

Site 410

Moscow, Moscow, Russia

Location

Site 415

Penza, 440026, Russia

Location

Site 407

Rostov-on-Don, 344022, Russia

Location

Site 405

Rostov-on-Don, 344037, Russia

Location

Site 411

Saint Petersburg, 194291, Russia

Location

Site 406

Saint Petersburg, 195067, Russia

Location

Site 402

Saint Petersburg, 196247, Russia

Location

Site 412

Saint Petersburg, 197022, Russia

Location

Site 403

Saint Petersburg, 197374, Russia

Location

Site 414

Saint Petersburg, 198205, Russia

Location

Site 401

Saint Petersburg, 198412, Russia

Location

Site 404

Saint Petersburg, 199106, Russia

Location

Site 413

Smolensk, 214018, Russia

Location

Site 502

Chernivtsi, 58001, Ukraine

Location

Site 506

Dnipro, 49005, Ukraine

Location

Site 505

Kharkiv, 61037, Ukraine

Location

Site 504

Kyiv, 2660, Ukraine

Location

Site 503

Kyiv, 4053, Ukraine

Location

Site 501

Lviv, 79059, Ukraine

Location

Site 507

Zaporizhzhia, 69600, Ukraine

Location

MeSH Terms

Interventions

omadacycline; Levofloxacin

Intervention Hierarchy (Ancestors)

Ofloxacin; Fluoroquinolones; 4-Quinolones; Quinolones; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

In May 2019, the DMC modified the randomization algorithm based on their review of the data. After this change, participants were randomized in a 1:1 ratio to either the omadacycline 200 iv/200 iv or levofloxacin arms.

Results Point of Contact

• Title: Paratek Medical Information
• Organization: Paratek Pharmaceuticals, Inc.

medinfo@paratekpharma.com

1-833-727-2835

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 27, 2018
• First Posted: November 28, 2018
• Study Start: November 19, 2018
• Primary Completion: June 26, 2019
• Study Completion: July 24, 2019
• Last Updated: July 7, 2020
• Results First Posted: July 7, 2020

Record last verified: 2020-07

Locations

GE (4); LA (5); RU (15); UA (7)