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Phase 1 N=14 Randomized Double-blind Treatment

Drug-drug Interaction Study of Gepotidacin

Infections, Bacterial

Enrolled (actual)
14
Serious AEs
0.0%
Results posted
Mar 2022
Primary outcome: Primary: Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma — 4.817; 4.548 Micrograms per milliliter

Study Design & Population

Study type
Interventional
Phase
Phase 1
Interventions
Gepotidacin (Drug); Cimetidine (Drug); Rifampicin (Drug); Midazolam (Drug); Digoxin (Drug); Placebo matching to gepotidacin (Other)
Age
Adult · 18+ yrs
Sex
All
Sponsor
GlaxoSmithKline
Primary completion
Dec 2020

Outcome Measures

OutcomeResultp-value
PRIMARY
Cohort 1: Maximum Observed Concentration (Cmax) of Gepotidacin in Plasma
4.817; 4.548
PRIMARY
Cohort 1: Time to Reach Maximum Observed Concentration (Tmax) of Gepotidacin in Plasma
2.500; 2.500
PRIMARY
Cohort 1: Terminal Phase Half-life (t1/2) of Gepotidacin in Plasma
11.344; 12.415
PRIMARY
Cohort 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Time of the Last Quantifiable Concentration (AUC [0-t]) of Gepotidacin in Plasma
20.3; 23.4
PRIMARY
Cohort 1: AUC From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) of Gepotidacin in Plasma
20.6; 23.9
PRIMARY
Cohort 2: Cmax of Gepotidacin in Plasma
3.735; 2.728
PRIMARY
Cohort 2: Lag Time Before Observation of Drug Concentrations (Tlag) of Gepotidacin in Plasma
0.000; 0.000
PRIMARY
Cohort 2: Tmax of Gepotidacin in Plasma
2.500; 2.000
PRIMARY
Cohort 2: AUC(0-t) of Gepotidacin in Plasma
19.0; 9.0
PRIMARY
Cohort 2: AUC(0-infinity) of Gepotidacin in Plasma
19.3; 9.3
PRIMARY
Cohort 3: Cmax of Digoxin in Plasma
1553.135; 2381.259
PRIMARY
Cohort 3: Tlag of Digoxin in Plasma
0.000; 0.000
PRIMARY
Cohort 3: Tmax of Digoxin in Plasma
2.000; 1.275
PRIMARY
Cohort 3: AUC(0-t) of Digoxin in Plasma
25353.1; 30842.3
PRIMARY
Cohort 3: AUC(0-infinity) of Digoxin in Plasma
30743.6; 34456.5
PRIMARY
Cohort 3: Cmax of Midazolam in Plasma
5.238; 6.507
PRIMARY
Cohort 3: Tlag of Midazolam in Plasma
0.000; 0.000
PRIMARY
Cohort 3: Tmax of Midazolam in Plasma
0.650; 0.500
PRIMARY
Cohort 3: AUC(0-t) of Midazolam in Plasma
23.3; 44.8
PRIMARY
Cohort 3: AUC(0-infinity) of Midazolam in Plasma
24.9; 47.4
PRIMARY
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
5.436; 5.143
PRIMARY
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma
2.000; 1.500
PRIMARY
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 24 Hours Post-dose (AUC[0-24]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
20.9; 19.0
PRIMARY
Cohort 4: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to the Concentration at 48 Hours Post-dose (AUC[0-48]) of Gepotidacin Following Single Dose of 1500 mg in Plasma
21.9; 20.0
PRIMARY
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma
21.9; 20.0
PRIMARY
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma
22.3; 20.4
PRIMARY
Cohort 4: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
11.204
PRIMARY
Cohort 4: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg -Fed State
2.000
PRIMARY
Cohort 4: AUC From Time 0 (Predose) to Time Tau (AUC[0-tau]) of Gepotidacin in Plasma After the First Dose of 3000 Mg-Fed State
37.3
PRIMARY
Cohort 4: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
12.363
PRIMARY
Cohort 4: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
2.000
PRIMARY
Cohort 4: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Evening Dose)-Fed State
46.7
PRIMARY
Cohort 4: Accumulation Ratio Based on Cmax (RoCmax) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
1.103
PRIMARY
Cohort 4: Accumulation Ratio Based on AUC(0-tau) (RoAUC) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)-Fed State
1.254
PRIMARY
Cohort 4: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
84.6
PRIMARY
Cohort 4: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
90.8
PRIMARY
Cohort 4: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
91.4
PRIMARY
Cohort 4: Number of Participants With Serious Adverse Events (SAE) and Non-serious Adverse Events (Non-SAE)
0; 0; 0; 0; 0; 1
PRIMARY
Cohort 4: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 0; 0; 3; 11
PRIMARY
Cohort 4: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 0; 0; 3; 11
PRIMARY
Cohort 4: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
3; 11; 11; 11; 0; 0
PRIMARY
Cohort 4: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 1; 0; 0; 3; 10
PRIMARY
Cohort 4: Number of Participants With Any Increase in Maximum Post-Baseline Electrocardiogram (ECG) Parameter Corrected QT (QTc) Interval
1; 8; 3; 9; 1; 1
PRIMARY
Cohort 4: Cmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
5.421; 5.158
PRIMARY
Cohort 4: Tlag of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
0.000; 0.000
PRIMARY
Cohort 4: Tmax of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
2.000; 1.500
PRIMARY
Cohort 4: AUC(0-t) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
21.9; 20.0
PRIMARY
Cohort 4: AUC(0-infinity) of Gepotidacin Following Single Dose of 1500 mg in Plasma - Food Effect in Japanese Participants
22.3; 20.4
SECONDARY
Cohort 1: AUC (0-24) of Gepotidacin in Plasma
19.3; 21.9
SECONDARY
Cohort 1: AUC(0-48) of Gepotidacin in Plasma
20.3; 23.0
SECONDARY
Cohort 1: Tlag of Gepotidacin in Plasma
0.000; 0.000
SECONDARY
Cohort 1: Apparent Volume of Distribution (Vz/F) of Gepotidacin in Plasma
1190.16; 1143.29
SECONDARY
Cohort 1: Apparent Oral Clearance (CL/F) of Gepotidacin in Plasma
72.72; 64.14
SECONDARY
Cohort 1: Total Unchanged Drug (Ae Total) of Gepotidacin in Urine
337.92; 410.10
SECONDARY
Cohort 1: AUC(0-24) of Gepotidacin in Urine
3292.1; 3612.4
SECONDARY
Cohort 1: AUC(0-48) of Gepotidacin in Urine
3578.2; 3831.1
SECONDARY
Cohort 1: Renal Clearance (CLr) of Gepotidacin
16.06; 17.59
SECONDARY
Cohort 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin
28.66; NA; 89.18; 142.99; 50.52; 82.77
SECONDARY
Cohort 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
22.72; 26.90
SECONDARY
Cohort 1: Number of Participants With SAE and Non-SAE
0; 0; 0; 0
SECONDARY
Cohort 1: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 14; 11; 0; 2
SECONDARY
Cohort 1: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 14; 11; 0; 2
SECONDARY
Cohort 1: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
14; 13; 0; 0; 14; 13
SECONDARY
Cohort 1: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 14; 13; 0; 0
SECONDARY
Cohort 1: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
3; 4; 0; 1
SECONDARY
Cohort 2: AUC(0-24) of Gepotidacin in Plasma
17.9; 8.9
SECONDARY
Cohort 2: AUC(0-48) of Gepotidacin in Plasma
19.0; 9.5
SECONDARY
Cohort 2: T1/2 of Gepotidacin in Plasma
10.882; 10.972
SECONDARY
Cohort 2: Vz/F of Gepotidacin in Plasma
1217.45; 2460.46
SECONDARY
Cohort 2: CL/F of Gepotidacin in Plasma
77.55; 155.43
SECONDARY
Cohort 2: Ae Total of Gepotidacin in Urine
312.73; 156.05
SECONDARY
Cohort 2: AUC(0-24) of Gepotidacin in Urine
3081.3; 1352.4
SECONDARY
Cohort 2: AUC(0-48) of Gepotidacin in Urine
3370.1; 1476.8
SECONDARY
Cohort 2: CLr of Gepotidacin
16.49; 17.07
SECONDARY
Cohort 2: Ae(t1-t2) of Gepotidacin
12.67; NA; 79.84; 55.81; 67.48; 21.66
SECONDARY
Cohort 2: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin
20.85; 10.42
SECONDARY
Cohort 2: Number of Participants With SAE and Non-SAE
0; 0; 0; 3; 2; 2
SECONDARY
Cohort 2: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 17; 16; 0; 1
SECONDARY
Cohort 2: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 17; 15; 0; 2
SECONDARY
Cohort 2: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
17; 16; 0; 0; 17; 16
SECONDARY
Cohort 2: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 16; 14; 1; 0
SECONDARY
Cohort 2: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
2; 2; 0; 1
SECONDARY
Cohort 3: Cmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
7.867
SECONDARY
Cohort 3: Tmax of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
2.500
SECONDARY
Cohort 3: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)
0.250
SECONDARY
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma First Dose of 3000 mg (First Dose)
29.8
SECONDARY
Cohort 3: Cmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
10.051
SECONDARY
Cohort 3: Tmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
2.000
SECONDARY
Cohort 3: AUC(0-tau) of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
41.9
SECONDARY
Cohort 3: RoCmax of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
1.278
SECONDARY
Cohort 3: RoAUC of Gepotidacin in Plasma After the Second Dose of 3000 mg (Second Dose)
1.406
SECONDARY
Cohort 3: AUC(0-24) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
73.2
SECONDARY
Cohort 3: AUC(0-48) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
81.2
SECONDARY
Cohort 3: AUC(0-t) of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
85.2
SECONDARY
Cohort 3: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
959.42
SECONDARY
Cohort 3: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)
69.99
SECONDARY
Cohort 3: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose+ Second Dose)
9.501
SECONDARY
Cohort 3: Minimum Observed Concentration (Cmin) of Digoxin in Plasma
44.127; 77.447
SECONDARY
Cohort 3: T1/2 of Digoxin in Plasma
39.367; 32.777
SECONDARY
Cohort 3: Vz/F of Digoxin in Plasma
923.75; 688.49
SECONDARY
Cohort 3: CL/F of Digoxin in Plasma
16.26; 14.51
SECONDARY
Cohort 3: Cmin of Midazolam in Plasma
0.192; 0.222
SECONDARY
Cohort 3: T1/2 of Midazolam in Plasma
5.320; 6.075
SECONDARY
Cohort 3: Vz/F of Midazolam in Plasma
615.36; 371.24
SECONDARY
Cohort 3: CL/F of Midazolam in Plasma
80.17; 42.16
SECONDARY
Cohort 3: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose )
1066.21
SECONDARY
Cohort 3: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
NA; 117.61; 103.11; 70.98; 67.42; 64.49
SECONDARY
Cohort 3: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
4770.8
SECONDARY
Cohort 3: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
14333.9
SECONDARY
Cohort 3: AUC (0-48) of Gepotidacin in Urine Following Two 3000 mg Doses (First Dose + Second Dose)
16682.1
SECONDARY
Cohort 3: Percentage of the Given Dose of Drug Excreted in Urine (fe%) Following Two 3000 mg Doses of Gepotidacin (First Dose + Second Dose )
17.77
SECONDARY
Cohort 3: CLr of Gepotidacin Following Two 3000 mg Doses (First Dose + Second Dose)
13.19
SECONDARY
Cohort 3: Number of Participants With SAE and Non-SAE
0; 0; 1; 11
SECONDARY
Cohort 3: Number of Participants With Worst Case Hematology Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 19; 18; 0; 0
SECONDARY
Cohort 3: Number of Participants With Worst Case Clinical Chemistry Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 19; 17; 0; 1
SECONDARY
Cohort 3: Number of Participants With Worst Case Urinalysis Results Relative to Normal Range Post-Baseline Relative to Baseline
19; 18; 0; 0; 19; 18
SECONDARY
Cohort 3: Number of Participants With Worst Case Vital Sign Results Relative to Normal Range Post-Baseline Relative to Baseline
0; 0; 19; 18; 0; 0
SECONDARY
Cohort 3: Number of Participants With Any Increase in Maximum Post-Baseline ECG Parameter QTc Interval
2; 5; 0; 0
SECONDARY
Cohort 4: T1/2 of Gepotidacin Following Single Dose of 1500 mg in Plasma
12.848; 12.540
SECONDARY
Cohort 4: Vz/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
1246.70; 1329.83
SECONDARY
Cohort 4: CL/F of Gepotidacin Following Single Dose of 1500 mg in Plasma
67.26; 73.50
SECONDARY
Cohort 4: Tlag of Gepotidacin in Plasma After the First Dose of 3000 mg (First Dose)-Fed State
SECONDARY
Cohort 4: Vz/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
1251.05
SECONDARY
Cohort 4: CL/F of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose)-Fed State
68.83
SECONDARY
Cohort 4: T1/2 of Gepotidacin in Plasma Following Two 3000 mg Doses (First Dose + Second Dose )-Fed State
12.599
SECONDARY
Cohort 4: Ae Total of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
293.50
SECONDARY
Cohort 4: Ae(t1-t2) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
NA; 102.23; 60.05; 31.61; 16.51; 17.16
SECONDARY
Cohort 4: AUC(0-24) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
2142.4
SECONDARY
Cohort 4: AUC(0-48) of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition in Urine
2293.7
SECONDARY
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) for Gepotidacin 1500 mg Under Fed Condition
19.57
SECONDARY
Cohort 4: CLr of Gepotidacin Following Single Dose of 1500 mg Under Fed Condition
13.42
SECONDARY
Cohort 4: Ae Total of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
1334.42
SECONDARY
Cohort 4: Ae(t1-t2) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
NA; 221.19; 103.68; 67.58; 65.06; 112.83
SECONDARY
Cohort 4: AUC(0-tau) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
4996.9
SECONDARY
Cohort 4: AUC(0-24) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
14729.5
SECONDARY
Cohort 4: AUC(0-48) of Gepotidacin in Urine Following Two 3000 mg Doses-Fed State
15768.2
SECONDARY
Cohort 4: Percentage of the Given Dose of Drug Excreted in Urine (fe%) of Gepotidacin Following Two 3000 mg Doses-Fed State
22.24
SECONDARY
Cohort 4: CLr of Gepotidacin Following Two 3000 mg Dose-Fed State
14.61

Summary

This study is a drug-drug interaction (DDI), pharmacokinetics (PK), safety and tolerability study in adult healthy participants, including Japanese cohort. This study is designed to assess co-administration of probe substrates with gepotidacin in study cohorts 1 to 3 and establishing PK and safety in Japanese participants in cohort 4. Food effect will also be evaluated in cohort 4.

Eligibility Criteria

Inclusion Criteria

  • Participant must be greater than or equal to (>=) 18 to less than or equal to (= =40 kilograms (kg) and body mass index within the range 18.5 to 32.0 kilograms per square meter (kg/m^2) (inclusive).
  • Male and/or female: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies.
  • Female participants: A female participant is eligible to participate if she is not pregnant or breastfeeding, and 1 of the following conditions applies: Is a woman of non-childbearing potential or Is a woman of childbearing potential (WOCBP) and using a contraceptive method that is highly effective, with a failure rate of 450 milliseconds (msec) at Screening or Check-in.
  • Presence of hepatitis B surface antigen or positive hepatitis C antibody test result at Screening or within 3 months prior to starting study intervention.
  • Alanine aminotransferase (ALT) >1.5 times upper limit of normal (ULN) at Screening or Check-in.
  • Bilirubin >1.5 times ULN (isolated bilirubin >1.5 times ULN is acceptable if bilirubin is fractionated and direct bilirubin 21 units (or an average daily intake of >3 units) for males or an average weekly intake of >14 units (or an average daily intake >2 units) for females. One unit is equivalent to 270 mL of full strength beer, 470 mL of light beer, 30 mL of spirits, or 100 mL of wine.
  • Cohort 3 Only: Digoxin-related exclusions include the following at Screening:

Serum potassium >5.5 milliequivalent per liter (mEq/L) or < 3.6 mEq/L Serum magnesium <1.6 milligrams per deciliter (mg/dL) Serum calcium (total) <8.5 mg/dL History of hypersensitivity to digoxin or other digitalis glycosides Any clinically relevant abnormality on 12-lead ECG at Screening or Check-in.

  • Participant has donated blood in excess of 500 mL within 12 weeks prior to dosing or participation in the study would result in donation of blood or blood products in excess of 500 mL within a 56-day period.
  • Participant is unable to comply with all study procedures, in the opinion of the investigator.
  • Participant should not participate in the study, in the opinion of the investigator or Sponsor.
View full record on ClinicalTrials.gov →

Data sourced from ClinicalTrials.gov (NCT04493931). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.

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