Comparison of Delafloxacin Versus Ceftriaxone for the Treatment of Uncomplicated Gonorrhea

• Sponsor: Melinta Therapeutics, Inc. (Industry)
• Overall Status: Terminated
• CT.gov ID: NCT02015637
• Collaborator: (none)
• Enrollment: 460
• Locations: 25
• Arms: 2
• Actual Duration (Months): 10.5
• Patients Per Site: 18.4
• Patients Per Site Per Month: 1.7

Study Details

Study Description

Brief Summary

The purpose of this study is to evaluate the effects of a single oral dose of delafloxacin versus a single intramuscular injection of ceftriaxone in subjects with uncomplicated cervical, urethral, rectal, or pharyngeal gonorrhea.

Condition or Disease	Intervention/Treatment	Phase
Gonorrhea	Drug: Delafloxacin; Drug: Ceftriaxone	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 460 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Comparative Evaluation of the Single-dose Efficacy of Oral Delafloxacin Versus the Single-dose Efficacy of an Intramuscular Injection of Ceftriaxone in Subjects With Uncomplicated Urogenital Gonorrhea
• Actual Study Start Date: Jan 23, 2014
• Actual Primary Completion Date: Nov 1, 2014
• Actual Study Completion Date: Dec 10, 2014

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Delafloxacin 900mg orally (2 x 450 mg tablets) administered once	Drug: Delafloxacin; single dose
Active Comparator: ceftriaxone Ceftriaxone 250 mg intramuscular injection administered once	Drug: Ceftriaxone; single dose

Outcome Measures

Primary Outcome Measures

1. Number of Subjects With Cure or Failure of Urogenital Gonorrhea at Test of Cure (TOC) in the Urogenital MITT (UMITT) Population [Day 7 (± 3 days)]

   Cure for the primary outcome measure was defined as the eradication of N. gonorrhoeae at TOC as determined by a negative culture obtained from the urogenital site, which was positive at study entry, and with no additional antibiotics with activity against N. gonorrhoeae being administered from study entry through TOC.

Secondary Outcome Measures

1. Number of Subjects With Cure or Failure of Urogenital Gonorrhea at Test of Cure (TOC) in the Urogenital Microbiologically Evaluable (UME) Population [Day 7 (± 3 days)]

   Cure for the seconday outcome measure was defined as the eradication of N. gonorrhoeae at TOC as determined by a negative culture obtained from the urogenital site, which was positive at study entry, and with no additional antibiotics with activity against N. gonorrhoeae being administered from study entry through TOC.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 15 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Subject is a male or female 15 years of age or older.

• Subject must have had 1 or more of the following occur:

1. gonorrhea with the nucleic acid amplification test (NAAT) or culture within the previous 14 days

2. unprotected genital contact within 14 days with a person confirmed to be infected with gonorrhea,

3. gram-negative present in urogenital gram strain or male subject must present with purulent urethritis or a female subject with must present with mucopurulent cervical discharge

• Subject agrees to avoid unprotected sexual contact in order to minimize the risk of gonorrhea reinfection

• Subject must be in good health (ie, based on medical history), as determined by the investigator.

• In the opinion of the investigator, the subject must be able and willing to comply with protocol requirements. The subject must agree to provide reliable, verifiable contact information and agree to return for the Test-of-Cure Visit.

• If a subject's age is 15 years to less than the legal age of consent,a written, voluntarily signed assent must be obtained from the subject and a written, voluntarily signed informed consent must be signed by the subject's parent or legal guardian before the initiation of any study related procedures, unless the Institutional Review Board (IRB)/Independent Ethics Committee (IEC) determines that parent/legal guardian consent is not required.

Exclusion Criteria:

• Confirmed, or suspected, complicated or systemic gonococcal infection, such as pelvic inflammatory disease, arthritis, or endocarditis.

• Subject has taken one of the following products within 6 hours of the Entry Visit that may interfere with the absorption of a quinolone antibiotic: magnesium/aluminum antacids; sucralfate; Videx® (didanosine) chewable/buffered tablets; other highly buffered drugs; or other products containing calcium, iron, or zinc.

• Use of systemic or intravaginal antibiotics that are potentially effective against gonorrhea 4 weeks prior to study drug administration.

• Subjects with a current or prior history of seizures, and subjects being treated with drugs that are known to have a sizable potential of or reduce the threshold for inducing seizures (eg, bupropion, theophylline, and tricyclic and tetracyclic antidepressants).

• Current use of systemic corticosteroid or immunosuppressive drugs.

• Known significant immunosuppression (eg, cluster of differentiation (CD4) cell count <200/mm3 or absolute neutrophil count <500/mL).

• Cytotoxic chemotherapy or radiation therapy during the previous 3 months.

• Subject is co-infected with an additional sexually transmitted disease (STD) for which treatment cannot be safely deferred until after the Test-of-Cure Visit unless the treatment is not potentially effective against gonorrhea.

• Subject has used an investigational drug or product within 30 days before study drug dosing.

• Medical history of Type 1 hypersensitivity to antibiotics of the quinolone or cephalosporin classes.

• Hysterectomized subjects without a cervix are ineligible.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Melinta 304 Study	Birmingham	Alabama	United States	35294
2	Melinta 304 Study Site	Chula Vista	California	United States	90911
3	Melinta 304 Study Site	La Mesa	California	United States	91942
4	Melinta 304 Study Site	Los Angeles	California	United States	90069
5	Melinta 304 Study Site	San Francisco	California	United States	94103
6	Melinta 304 Study	Atlanta	Georgia	United States	30308
7	Melinta 304 Study	Decatur	Georgia	United States	30033
8	Melinta 304 Study Site	Indianapolis	Indiana	United States	46202
9	Melinta 304 Study Site	New Orleans	Louisiana	United States	70112
10	Melinta 304 Study Site	Omaha	Nebraska	United States	68114
11	Melinta 304 Study Site	Las Vegas	Nevada	United States	89109
12	Melinta 304 Study Site	Bronx	New York	United States	100461
13	Melinta 304 Study Site	Brooklyn	New York	United States	11203
14	Melinta 304 Study	Brooklyn	New York	United States	11203
15	Melinta 304 Study Site	New York	New York	United States	10018
16	Melinta 304 Study Site	Durham	North Carolina	United States	27701
17	Melinta 304 Study Site	Greensboro	North Carolina	United States	27405
18	Melinta 304 Study Site	Cleveland	Ohio	United States	44108
19	Melinta 304 Study Site	Columbus	Ohio	United States	43231
20	Melinta 304 Study Site	Portland	Oregon	United States	97204
21	Melinta 304 Study	Erie	Pennsylvania	United States	16507
22	Melinta 304 Study Site	Philadelphia	Pennsylvania	United States	191007
23	Melinta 304 Study Site	Pittsburgh	Pennsylvania	United States	15213
24	Melinta 304 Study Site	Houston	Texas	United States	77011
25	Melinta 304 Study Site	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Melinta Therapeutics, Inc.

Investigators

• Study Director: Sue Cammarata, MD, Melinta Therapeutics, Inc.

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Melinta Therapeutics, Inc.
• ClinicalTrials.gov Identifier: NCT02015637
• Other Study ID Numbers: ML-3341-304
• First Posted: Dec 19, 2013
• Last Update Posted: Jun 20, 2018
• Last Verified: May 1, 2018

• Keywords provided by Melinta Therapeutics, Inc.: Gonorrhea; N. gonorrhoeae; bacterial infection; Anti-Infective Agents; Anti-Bacterial Agents
• Additional relevant MeSH terms: Gonorrhea; Ceftriaxone

Study Results

Participant Flow

Arm/Group Title	Delafloxacin	Ceftriaxone
Arm/Group Description	900mg orally (2 x 450 mg tablets) administered once Delafloxacin: single dose	Ceftriaxone 250 mg intramuscular injection administered once Ceftriaxone: single dose
Period Title: Overall Study
STARTED	306	154
COMPLETED	298	149
NOT COMPLETED	8	5

Baseline Characteristics

Arm/Group Title	Delafloxacin	Ceftriaxone	Total
Arm/Group Description	900mg orally (2 x 450 mg tablets) administered once Delafloxacin: single dose	Ceftriaxone 250 mg intramuscular injection administered once Ceftriaxone: single dose	Total of all reporting groups
Overall Participants	304	154	458
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.7 (8.82)	28.7 (10.04)	29.3 (9.25)
Age, Customized (Count of Participants)
<18 year	1 0.3%	2 1.3%	3 0.7%
18-70 years	303 99.7%	152 98.7%	455 99.3%
Sex/Gender, Customized (Count of Participants)
Were heterosexul	132 43.4%	59 38.3%	191 41.7%
Had sex with men or were bisexual	112 36.8%	60 39%	172 37.6%
Missing	1 0.3%	0 0%	1 0.2%
Sex: Female, Male (Count of Participants)
Female	59 19.4%	35 22.7%	94 20.5%
Male	245 80.6%	119 77.3%	364 79.5%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	34 11.2%	22 14.3%	56 12.2%
Not Hispanic or Latino	268 88.2%	131 85.1%	399 87.1%
Unknown or Not Reported	2 0.7%	1 0.6%	3 0.7%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	1 0.3%	0 0%	1 0.2%
Asian	7 2.3%	1 0.6%	8 1.7%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	186 61.2%	92 59.7%	278 60.7%
White	98 32.2%	48 31.2%	146 31.9%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	12 3.9%	13 8.4%	25 5.5%
Positive culture for Gonorrhea (GC) (Count of Participants)
Count of Participants [Participants]	239 78.6%	107 69.5%	346 75.5%

Outcome Measures

1. Primary Outcome

Title	Number of Subjects With Cure or Failure of Urogenital Gonorrhea at Test of Cure (TOC) in the Urogenital MITT (UMITT) Population
Description	Cure for the primary outcome measure was defined as the eradication of N. gonorrhoeae at TOC as determined by a negative culture obtained from the urogenital site, which was positive at study entry, and with no additional antibiotics with activity against N. gonorrhoeae being administered from study entry through TOC.
Time Frame	Day 7 (± 3 days)

Outcome Measure Data

Analysis Population Description

The primary efficacy analysis was done on the UMITT population, which included all subjects in the ITT analysis set who had a positive culture for N gonorrhoeae obtained at a urogenital site at the Entry Visit, and who did not receive antibiotic therapy for a C trachomatis infection that was potentially effective against N gonorrhoeae prior to TOC.

Arm/Group Title	Delafloxacin	Ceftriaxone
Arm/Group Description	900mg orally (2 x 450 mg tablets) administered once Delafloxacin: single dose	Ceftriaxone 250 mg intramuscular injection administered once Ceftriaxone: single dose
Measure Participants	228	100
Cure	194 63.8%	91 59.1%
Failure	34 11.2%	9 5.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delafloxacin, Ceftriaxone
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Two-sided 95% confidence intervals (CIs) using the Wald test was constructed for comparisons between delafloxacin and ceftriaxone. A hierarchical approach was implemented for the primary and secondary analyses to control for the overall type 1 error rate of 0.05 due to multiple comparisons.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in cure rate
	Estimated Value	-5.9
	Confidence Interval	(2-Sided) 95%; -13.18 to 1.36
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Number of Subjects With Cure or Failure of Urogenital Gonorrhea at Test of Cure (TOC) in the Urogenital Microbiologically Evaluable (UME) Population
Description	Cure for the seconday outcome measure was defined as the eradication of N. gonorrhoeae at TOC as determined by a negative culture obtained from the urogenital site, which was positive at study entry, and with no additional antibiotics with activity against N. gonorrhoeae being administered from study entry through TOC.
Time Frame	Day 7 (± 3 days)

Outcome Measure Data

Analysis Population Description

Urogenital ME (UME): All subjects included in the UMITT analysis set who received study drug and had no important protocol deviations that would affect the assessment of efficacy

Arm/Group Title	Delafloxacin	Ceftriaxone
Arm/Group Description	900mg orally (2 x 450 mg tablets) administered once Delafloxacin: single dose	Ceftriaxone 250 mg intramuscular injection administered once Ceftriaxone: single dose
Measure Participants	226	95
Cure	194 63.8%	91 59.1%
Failure	32 10.5%	4 2.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Delafloxacin, Ceftriaxone
	Comments
	Type of Statistical Test	Non-Inferiority
	Comments	Two-sided 95% confidence intervals (CIs) using the Wald test was constructed for comparisons between delafloxacin and ceftriaxone. A hierarchical approach was implemented for the primary and secondary analyses to control for the overall type 1 error rate of 0.05 due to multiple comparisons.
Statistical Test of Hypothesis	p-Value
	Comments
	Method
	Comments
Method of Estimation	Estimation Parameter	Difference in cure rates
	Estimated Value	-9.9
	Confidence Interval	(2-Sided) 95%; -16.03 to -3.87
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	All Adverse Events (AEs) occurring from the time the subject signed the Informed Consent Form (ICF) through the follow-up phone contact were reported and followed to resolution. Collection of all AEs occurred from the time the subject received study drug (Day 1) through the TOC visit (Day 7 +/- 3), or up to 10 days. Only Serious Adverse Events (SAEs) were collected after the TOC visit through the follow-up phone contact (Day 30 +/- 3 days), or up to 33 days.
Adverse Event Reporting Description	AEs were reported in the Safety Population which was defined as all subjects that received study drug. Two patients that were in the ITT population (all subjects randomly assigned to a treatment group) for delafloxacin did not receive study drug.
Arm/Group Title	Delafloxacin		Ceftriaxone
Arm/Group Description	900mg orally (2 x 450 mg tablets) administered once Delafloxacin: single dose		Ceftriaxone 250 mg intramuscular injection administered once Ceftriaxone: single dose
All Cause Mortality
	Delafloxacin		Ceftriaxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/304 (0%)		0/154 (0%)
Serious Adverse Events
	Delafloxacin		Ceftriaxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/304 (0%)		1/154 (0.6%)
Musculoskeletal and connective tissue disorders
Ankle fracture	0/304 (0%)		1/154 (0.6%)
Other (Not Including Serious) Adverse Events
	Delafloxacin		Ceftriaxone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	121/304 (39.8%)		13/154 (8.4%)
Gastrointestinal disorders
Diarrhea	97/304 (31.9%)		11/154 (7.1%)
Nausea	24/304 (7.9%)		2/154 (1.3%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

Melinta has the right to first publication of results, which would be made in conjunction with the PIs from all appropriate sites. Thereafter, PIs may publish results provided the PI submits the proposed publication to Melinta for review at least 60 days prior to the date of the proposed publication. Melinta may remove any information that is considered confidential and/or proprietary. If a publication is not submitted within 12 months of study conclusion, the PI may publish results.