Trial Outcomes & Findings for Finafloxacin for the Treatment of cUTI and/or Acute Pyelonephritis (NCT NCT01928433)

NCT ID: NCT01928433

Last Updated: 2017-06-20

Results Overview

The primary endpoint of this study is the clinical and microbiological response of patients with cUTI or pyelonephritis to treatment with finafloxacin for 5 days versus finafloxacin for 10 days versus ciprofloxacin for 10 days as a reference comparator at the Test of Cure (ToC) visit (Day 17) in the microbiological intent-to-treat population (micro-ITT population). Clinical response is defined as resolution of the symptoms of cUTI present at trial entry and no new symptoms developed. Microbiological response is defined as elimination or reduction of study entry pathogens to ≤ 10e3 CFU/mL on urine culture. The clinical and microbiological response will be assessed for each group on Day 17 and will be compared between the three groups to assess the efficacy in each group.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

225 participants

Primary outcome timeframe

Day 17

Results posted on

2017-06-20

Participant Flow

Participant milestones

Participant milestones
Measure	Finafloxacin 5 Days Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
Overall Study STARTED	76	75	74
Overall Study COMPLETED	56	54	46
Overall Study NOT COMPLETED	20	21	28

Reasons for withdrawal

Reasons for withdrawal
Measure	Finafloxacin 5 Days Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
Overall Study Adverse Event	5	2	5
Overall Study Protocol Violation	0	0	2
Overall Study Lack of Efficacy	5	4	4
Overall Study Withdrawal by Subject	0	4	0
Overall Study Negative screening urine culture	7	6	10
Overall Study Lost to Follow-up	0	2	3
Overall Study Other reasons	3	3	4

Baseline Characteristics

Finafloxacin for the Treatment of cUTI and/or Acute Pyelonephritis

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Finafloxacin 5 Days n=76 Participants Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=75 Participants Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=72 Participants Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily	Total n=223 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	52 Participants n=5 Participants	43 Participants n=7 Participants	48 Participants n=5 Participants	143 Participants n=4 Participants
Age, Categorical >=65 years	24 Participants n=5 Participants	32 Participants n=7 Participants	24 Participants n=5 Participants	80 Participants n=4 Participants
Age, Continuous	54.6 years STANDARD_DEVIATION 19.63 • n=5 Participants	58.0 years STANDARD_DEVIATION 19.28 • n=7 Participants	51.0 years STANDARD_DEVIATION 21.01 • n=5 Participants	54.6 years STANDARD_DEVIATION 20.08 • n=4 Participants
Sex: Female, Male Female	64 Participants n=5 Participants	62 Participants n=7 Participants	57 Participants n=5 Participants	183 Participants n=4 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	13 Participants n=7 Participants	15 Participants n=5 Participants	40 Participants n=4 Participants
Region of Enrollment Germany	10 participants n=5 Participants	14 participants n=7 Participants	7 participants n=5 Participants	31 participants n=4 Participants
Region of Enrollment Poland	66 participants n=5 Participants	61 participants n=7 Participants	65 participants n=5 Participants	192 participants n=4 Participants

PRIMARY outcome

Timeframe: Day 17

Population: The micro-ITT population is composed of all randomized patients who have a baseline bacterial pathogen on culture of urine or blood that causes UTI against which the investigational drug has antibacterial activity.

Outcome measures

Outcome measures
Measure	Finafloxacin 5 Days n=64 Participants Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=68 Participants Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=61 Participants Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
Number of Participants With Clinical and Microbiological Response	45 Participants	46 Participants	35 Participants

SECONDARY outcome

Timeframe: Day 3

The clinical and microbiological response as the efficacy parameter will be assessed for each group and will be compared between the three groups. Separate analyses will be performed for all time points for the clinical and microbiological responders and compared also between the different groups.

Outcome measures

Outcome measures
Measure	Finafloxacin 5 Days n=64 Participants Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=68 Participants Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=61 Participants Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
Number of Participants With Clinical and Microbiological Response at the On Therapy (OT) Visit (Day 3).	39 Participants	40 Participants	33 Participants

SECONDARY outcome

Timeframe: Day 10

Outcome measures

Outcome measures
Measure	Finafloxacin 5 Days n=64 Participants Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=68 Participants Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=61 Participants Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
Number of Participants With Clinical and Microbiological Response at the End of Therapy (EoT) Visit (Day 10).	49 Participants	49 Participants	44 Participants

SECONDARY outcome

Timeframe: Day 24

Outcome measures

Outcome measures
Measure	Finafloxacin 5 Days n=64 Participants Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=68 Participants Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=61 Participants Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
Number of Participants With Clinical and Microbiological Response at the End of Study (EoS) Visit (Day 24).	47 Participants	42 Participants	34 Participants

SECONDARY outcome

Timeframe: Screening to Day 24

Population: Safety (SAF) population includes all subjects with at least one administration of study drug.

This study will evaluate the safety of the different regimens of finafloxacin. The safety outcome measures assessed are the following: vital signs, physical examinations, ECGs, haematology, biochemistry, urinalysis, adverse events and serious adverse events. Adverse events and serious adverse events will be documented throughout the study for each group (including comparator group and the incidence and severity of their occurrence will be compared between all groups. The results of all other safety outcome measures will be compared with the baseline values of each group to determine if significant changes occurred during the course of the study within one group. The results at the different visits will also be compared between the groups to identify significant differences between the 3 treatment groups.

Outcome measures

Outcome measures
Measure	Finafloxacin 5 Days n=76 Participants Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=75 Participants Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=72 Participants Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
The Safety and Tolerability of Multiple Doses of Finafloxacin: Number of Treatment-emergent Adverse Events	70 Treatment-emergent AEs	51 Treatment-emergent AEs	70 Treatment-emergent AEs

SECONDARY outcome

Timeframe: Screening to day 24

Population: Safety (SAF) population includes all subjects with at least one administration of study drug.

Outcome measures

Outcome measures
Measure	Finafloxacin 5 Days n=76 Participants Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=75 Participants Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=72 Participants Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
The Safety and Tolerability of Multiple Doses of Finafloxacin: Number of Participants Who Discontinued Due to TEAE	7 Participants	2 Participants	4 Participants

Adverse Events

Finafloxacin 5 Days

Serious events: 3 serious events

Other events: 29 other events

Deaths: 0 deaths

Finafloxacin 10 Days

Serious events: 4 serious events

Other events: 19 other events

Deaths: 0 deaths

Ciprofloxacin 10 Days

Serious events: 1 serious events

Other events: 29 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Finafloxacin 5 Days n=76 participants at risk Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=75 participants at risk Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=72 participants at risk Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
Renal and urinary disorders Obstructive uropathy	0.00% 0/76 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/75 • From screening to end-of-study visit, 24 - 28 days.	1.4% 1/72 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.
Gastrointestinal disorders Acute gastritis	1.3% 1/76 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/75 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/72 • From screening to end-of-study visit, 24 - 28 days.
Infections and infestations Pyonephrosis	0.00% 0/76 • From screening to end-of-study visit, 24 - 28 days.	1.3% 1/75 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/72 • From screening to end-of-study visit, 24 - 28 days.
Skin and subcutaneous tissue disorders Perioral dermatitis	1.3% 1/76 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/75 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/72 • From screening to end-of-study visit, 24 - 28 days.
Gastrointestinal disorders Diarrhoea	1.3% 1/76 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	1.3% 1/75 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/72 • From screening to end-of-study visit, 24 - 28 days.
Infections and infestations Clostridium difficile infection	0.00% 0/76 • From screening to end-of-study visit, 24 - 28 days.	2.7% 2/75 • Number of events 2 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/72 • From screening to end-of-study visit, 24 - 28 days.
Musculoskeletal and connective tissue disorders Ovarian mucinous cystadenoma	0.00% 0/76 • From screening to end-of-study visit, 24 - 28 days.	1.3% 1/75 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/72 • From screening to end-of-study visit, 24 - 28 days.

Other adverse events

Other adverse events
Measure	Finafloxacin 5 Days n=76 participants at risk Finafloxacin (i.v. and oral) for a total of 5 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Finafloxacin 10 Days n=75 participants at risk Finafloxacin (i.v. and oral) for a total of 10 days. Finafloxacin 800 mg i.v. once daily Finafloxacin 800 mg tablets (as four 200 mg tablets) once daily Ciprofloxacin placebo i.v. two times daily Ciprofloxacin placebo oral (as two capsules each) two times daily	Ciprofloxacin 10 Days n=72 participants at risk Ciprofloxacin (i.v. and oral) for a total of 10 days. Finafloxacin placebo i.v. once daily Finafloxacin placebo tablets (as four tablets) once daily Ciprofloxacin 400 mg i.v. two times daily Ciprofloxacin 500 mg oral (as two 250 mg capsules) two times daily
Gastrointestinal disorders Diarrhoea	5.3% 4/76 • Number of events 5 • From screening to end-of-study visit, 24 - 28 days.	4.0% 3/75 • Number of events 5 • From screening to end-of-study visit, 24 - 28 days.	6.9% 5/72 • Number of events 5 • From screening to end-of-study visit, 24 - 28 days.
Gastrointestinal disorders Abdominal pain	2.6% 2/76 • Number of events 2 • From screening to end-of-study visit, 24 - 28 days.	1.3% 1/75 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	4.2% 3/72 • Number of events 3 • From screening to end-of-study visit, 24 - 28 days.
Gastrointestinal disorders Nausea	6.6% 5/76 • Number of events 5 • From screening to end-of-study visit, 24 - 28 days.	1.3% 1/75 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	1.4% 1/72 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.
Investigations Blood pressure increased	0.00% 0/76 • From screening to end-of-study visit, 24 - 28 days.	5.3% 4/75 • Number of events 5 • From screening to end-of-study visit, 24 - 28 days.	2.8% 2/72 • Number of events 3 • From screening to end-of-study visit, 24 - 28 days.
Metabolism and nutrition disorders Hypokalaemia	3.9% 3/76 • Number of events 3 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/75 • From screening to end-of-study visit, 24 - 28 days.	2.8% 2/72 • Number of events 2 • From screening to end-of-study visit, 24 - 28 days.
Nervous system disorders Headache	7.9% 6/76 • Number of events 7 • From screening to end-of-study visit, 24 - 28 days.	4.0% 3/75 • Number of events 3 • From screening to end-of-study visit, 24 - 28 days.	8.3% 6/72 • Number of events 9 • From screening to end-of-study visit, 24 - 28 days.
Psychiatric disorders Insomnia	3.9% 3/76 • Number of events 4 • From screening to end-of-study visit, 24 - 28 days.	2.7% 2/75 • Number of events 2 • From screening to end-of-study visit, 24 - 28 days.	1.4% 1/72 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.
Musculoskeletal and connective tissue disorders Back pain	1.3% 1/76 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	2.7% 2/75 • Number of events 3 • From screening to end-of-study visit, 24 - 28 days.	1.4% 1/72 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.
Gastrointestinal disorders Constipation	2.6% 2/76 • Number of events 2 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/75 • From screening to end-of-study visit, 24 - 28 days.	2.8% 2/72 • Number of events 2 • From screening to end-of-study visit, 24 - 28 days.
Vascular disorders Thrombophlebitis superficial	0.00% 0/76 • From screening to end-of-study visit, 24 - 28 days.	1.3% 1/75 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	4.2% 3/72 • Number of events 3 • From screening to end-of-study visit, 24 - 28 days.
Gastrointestinal disorders Vomitting	3.9% 3/76 • Number of events 3 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/75 • From screening to end-of-study visit, 24 - 28 days.	1.4% 1/72 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.
Nervous system disorders Sciatica	1.3% 1/76 • Number of events 1 • From screening to end-of-study visit, 24 - 28 days.	2.7% 2/75 • Number of events 2 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/72 • From screening to end-of-study visit, 24 - 28 days.
General disorders Injection site hypersensitivity	0.00% 0/76 • From screening to end-of-study visit, 24 - 28 days.	0.00% 0/75 • From screening to end-of-study visit, 24 - 28 days.	2.8% 2/72 • Number of events 2 • From screening to end-of-study visit, 24 - 28 days.

Additional Information

Prof. Dr. med. Florian Wagenlehner

Universityhospital Gießen and Marburg, Germany

Phone: +49-641-98544516

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place