Trial Outcomes & Findings for A Dose-Ranging Study Evaluating the Efficacy, Safety, and Tolerability of GSK2140944 in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria Gonorrhoeae (NCT NCT02294682)

Last Updated: 2017-05-23

Results Overview

Pre-treatment urogenital, pharyngeal, and rectal swab specimens were obtained for bacteriological culture for neisseria (N.) gonorrhoeae at the Baseline visit. Test- of-Cure was defined by infection site (that is urogenital and, as appropriate, rectal and/or pharyngeal) as culture confirmed bacterial eradication of N. gonorrhoeae observed 3 to 7 days post-treatment. Pre-treatment urogenital specimens were obtained for nucleic acid amplification test (NAAT) assay to detect the presence of N. gonorrhoeae and chlamydia trachomatis at the Baseline visit. Only participants who had a pre-therapy N. gonorrhoeae isolate recovered from their urogenital specimen were evaluated. Microbiologically evaluable (ME) Population comprised of all randomized participants who had N. gonorrhoeae isolated from Baseline cultures of urogenital swab specimens, received any dose of gepotidacin, and returned for their TOC visit.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

106 participants

Primary outcome timeframe

Baseline (Day 1, pre-dose) and Test-of-Cure visit (Day 4 to 8)

Results posted on

2017-05-23

Participant Flow

This was a phase II, randomized, multicenter, open-label, dose ranging study evaluating the efficacy, safety and tolerability of gepotidacin therapy in participants with uncomplicated urogenital gonorrhea. The study duration was approximately 1 week with 2 planned study visits: Baseline (Day 1, pre-dose) and Test-of-Cure (TOC) (Day 4 to 8) visit.

A total of 106 participants (par.) were randomized to receive GSK2140944 1500 milligrams (mg) or GSK2140944 3000 mg, of which 105 participants received any dose of study treatment and 1 par. was unable to swallow the capsule; therefore, did not receive study drug.

Participant milestones

Participant milestones
Measure	GSK2140944 1500 mg Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.
Overall Study STARTED	53	53
Overall Study COMPLETED	52	53
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	GSK2140944 1500 mg Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.
Overall Study Could not swallow pills	1	0

Baseline Characteristics

A Dose-Ranging Study Evaluating the Efficacy, Safety, and Tolerability of GSK2140944 in the Treatment of Uncomplicated Urogenital Gonorrhea Caused by Neisseria Gonorrhoeae

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	GSK2140944 1500 mg n=53 Participants Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg n=53 Participants Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	Total n=106 Participants Total of all reporting groups
Age, Continuous	34.1 Years STANDARD_DEVIATION 11.45 • n=93 Participants	32.4 Years STANDARD_DEVIATION 11.33 • n=4 Participants	33.3 Years STANDARD_DEVIATION 11.37 • n=27 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants
Sex: Female, Male Male	50 Participants n=93 Participants	51 Participants n=4 Participants	101 Participants n=27 Participants
Race/Ethnicity, Customized African American/African Heritage (Heri.)	22 Participants n=93 Participants	25 Participants n=4 Participants	47 Participants n=27 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	1 Participants n=93 Participants	1 Participants n=4 Participants	2 Participants n=27 Participants
Race/Ethnicity, Customized Central/South Asian Heritage	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Japanese/East Asian Heri. /South East Asian Heri.	1 Participants n=93 Participants	0 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Native Hawaiian or other Pacific Islander	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized White	24 Participants n=93 Participants	21 Participants n=4 Participants	45 Participants n=27 Participants
Race/Ethnicity, Customized White & African American/African Heritage	0 Participants n=93 Participants	1 Participants n=4 Participants	1 Participants n=27 Participants
Race/Ethnicity, Customized Unknown	5 Participants n=93 Participants	3 Participants n=4 Participants	8 Participants n=27 Participants

PRIMARY outcome

Timeframe: Baseline (Day 1, pre-dose) and Test-of-Cure visit (Day 4 to 8)

Population: ME Population

Outcome measures

Outcome measures
Measure	GSK2140944 1500 mg n=30 Participants Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg n=39 Participants Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.
Number of Participants With Culture-confirmed Bacterial Eradication of Urogenital Neisseria Gonorrhoeae at the Test-of-Cure Visit	29 Participants	37 Participants

SECONDARY outcome

Timeframe: From start of the study treatment until Test-of-Cure visit (Day 4 to 8)

Population: Safety Population: comprised of all randomized participants who received any dose of study medication.

An AE is any untoward medical occurrence in a clinical investigation participants, temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product. SAE is any untoward event resulting in death, life threatening, requires hospitalization or prolongation of existing hospitalization, results in disability/incapacity, congenital anomaly/birth defect, any other situation according to medical or scientific judgment or all events of possible drug-induced liver injury with hyperbilirubinaemia (defined as alanine aminotransferase \[ALT\] \>=3 times upper limit of normal \[ULN\] and bilirubin \>=2 times ULN \[\>35 percent direct\] \[or ALT \>=3 times ULN and international normalization ratio INR\>1.5, if INR is measured\].

Outcome measures

Outcome measures
Measure	GSK2140944 1500 mg n=52 Participants Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg n=53 Participants Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any AE	27 Participants	34 Participants
Number of Participants With Any Adverse Event (AE) or Serious Adverse Event (SAE) Any SAE	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Baseline visit (Day 1) and Day 4 to Day 8

Population: Safety Population

BP was measured in semi-supine position after 5 minutes rest. It was recorded at Baseline visit, 2 hour post-dose visit for participants enrolled under orignal protocol, 0.5 hour post-dose for participants enrolled under protocol amendement 1 and up to TOC visit (Day 4 to 8).Vital sign measurements were obtained prior to any scheduled blood collection visit on the same assessment day. Baseline was defined as the study assessment on Day 1 (pre-dose). Change from Baseline was calculated as TOC visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	GSK2140944 1500 mg n=52 Participants Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg n=53 Participants Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points Systolic BP, Day 1, 2 hr post-dose, n=47, 48	0.4 Millimeter of mercury (mmHg) Standard Deviation 11.61	1.3 Millimeter of mercury (mmHg) Standard Deviation 11.97
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points Systolic BP, Day 4 to 8, n=52, 53	-2.8 Millimeter of mercury (mmHg) Standard Deviation 13.11	0.5 Millimeter of mercury (mmHg) Standard Deviation 11.73
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points Diastolic BP, Day 1, 2 hr post-dose, n=47, 48	0.1 Millimeter of mercury (mmHg) Standard Deviation 7.61	-0.9 Millimeter of mercury (mmHg) Standard Deviation 8.40
Change From Baseline in Systolic and Diastolic Blood Pressure (BP) at the Indicated Time Points Diastolic BP, Day 4 to 8, n=52, 53	-2.3 Millimeter of mercury (mmHg) Standard Deviation 8.73	-2.2 Millimeter of mercury (mmHg) Standard Deviation 9.86

SECONDARY outcome

Timeframe: Baseline visit (Day 1) and Day 4 to Day 8

Population: Safety Population

Pulse rate was measured in semi-supine position after 5 minutes rest. It was recorded at Baseline visit, 2 hour post-dose visit for participants enrolled under orignal protocol, 0.5 hour post-dose for participants enrolled under protocol amendement 1 and up to TOC visit (Day 4 to 8). Vital sign measurements were obtained prior to any scheduled blood collection visit on the same assessment day. Baseline was defined as the study assessment on Day 1 (pre-dose). Change from Baseline was calculated as TOC visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	GSK2140944 1500 mg n=52 Participants Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg n=53 Participants Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.
Change From Baseline in Pulse Rate at the Indicated Time Points Pulse rate Day 1, 2 hr post-dose, n=47, 48	-0.3 Beats per minute Standard Deviation 12.20	-1.4 Beats per minute Standard Deviation 8.72
Change From Baseline in Pulse Rate at the Indicated Time Points Pulse rate, Day 4 to 8, n=52, 53	1.1 Beats per minute Standard Deviation 11.92	2.2 Beats per minute Standard Deviation 14.12

SECONDARY outcome

Timeframe: Baseline visit (Day 1) and Day 4 to Day 8

Population: Safety Population

Temperature was measured in semi-supine position after 5 minutes rest. It was recorded at Baseline visit, 2 hour post-dose visit for participants enrolled under orignal protocol, 0.5 hour post-dose for participants enrolled under protocol amendement 1 and up to TOC visit (Day 4 to 8). Vital sign measurements were obtained prior to any scheduled blood collection visit on the same assessment day. Baseline was defined as the study assessment on Day 1 (pre-dose). Change from Baseline was calculated as TOC visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	GSK2140944 1500 mg n=52 Participants Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg n=53 Participants Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.
Change From Baseline in Temperature at the Indicated Time Points Temperature, Day 1, 2 hr post-dose, n=47, 48	-0.126 Celsius Standard Deviation 0.4327	-0.052 Celsius Standard Deviation 0.3664
Change From Baseline in Temperature at the Indicated Time Points Temperature, Day 4 to 8, n=52, 53	-0.121 Celsius Standard Deviation 0.4953	-0.088 Celsius Standard Deviation 0.3742

SECONDARY outcome

Timeframe: Baseline visit (Day 1) and Day 4 to Day 8

Population: Safety Population

Respiratory rate was measured in semi-supine position after 5 minutes rest. It was recorded at Baseline visit, 2 hour post-dose visit for participants enrolled under orignal protocol, 0.5 hour post-dose for participants enrolled under protocol amendement 1 and up to TOC visit (Day 4 to 8). Vital sign measurements was obtained prior to any scheduled blood collection visit on the same assessment day. Baseline was defined as the study assessment on Day 1 (pre-dose). Change from Baseline was calculated as TOC Visit value minus value at Baseline. Only those participants available at the specified time points were analyzed (represented by n=X, X in the category titles).

Outcome measures

Outcome measures
Measure	GSK2140944 1500 mg n=52 Participants Participants were randomized to receive oral dose of GSK2140944 1500 mg (3 immediate-release capsules of 500 mg each) with food and 240 milliliters (mL) of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.	GSK2140944 3000 mg n=53 Participants Participants were randomized to receive oral dose of GSK2140944 3000 mg (6 immediate-release capsules of 500 mg each) with food and 240 mL of water. Additional 100 mL of water was given to assist in swallowing a large number of capsules. Participants who tested positive for chlamydia trachomatis at the Baseline visit, received a single 1 gram dose of azithromycin or local standard of care at the TOC visit.
Change From Baseline in Respiratory Rate at the Indicated Time Points Respiratory rate, Day 1, 2 hr post-dose, n=47, 48	-0.1 Breaths per minute Standard Deviation 1.39	-0.3 Breaths per minute Standard Deviation 1.51
Change From Baseline in Respiratory Rate at the Indicated Time Points Respiratory rate, Day 4 to 8, n=52, 53	0.1 Breaths per minute Standard Deviation 1.66	-0.1 Breaths per minute Standard Deviation 1.61

SECONDARY outcome

Timeframe: Baseline visit and up to Day 8

Population: Safety Population

A single 12-lead ECGs were obtained at the Baseline, 2 hour post-dose, and at the TOC (Day 4 to 8) visit using an ECG machine that automatically calculates the heart rate and measures PR, QRS, QT, and corrected QT (QTc) intervals. ECG was obtained prior to any vital sign measurements or blood draws scheduled on the same assessment day. For participants enrolled under protocol amendment 1, ECG was measured at Baseline visit Day 1 (pre-dose) only. ECG assessments were presented as abnormal-clinically significant (CS) and abnormal-not clinically significant (NCS) at the indicated time points. Only those participants available at the specified time points were analyzed (represented by n=X , X in the category titles).