Phase 1
Completed N=16
Pharmacokinetics of Gepotidacin Tablets in Adults and Adolescents Subjects
Infections, Bacterial
Source: ClinicalTrials.gov NCT04079790 ↗
Enrolled (actual)
16
Serious AEs
0.0%
Results posted
Sep 2020
Primary outcomePrimary: Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Time of the Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of Gepotidacin 1500 mg — 19.69 Hours*micrograms per milliliter
Summary
This is double-blind, randomized, sequential, two part study. Part 1 is a 3 periods, fixed-sequence study and will be conducted to evaluate the pharmacokinetics, safety, and tolerability of the gepotidacin tablet in healthy adult subjects. Part 2 is a 2 periods, fixed-sequence study and will evaluate the pharmacokinetics, safety, and tolerability of the gepotidacin tablet in healthy adolescent subjects. The primary purpose of Part 1 is to evaluate the pharmacokinetics of a single 1500 milligram (mg) dose and two 3000 mg doses of gepotidacin given 6 and 12 hours apart in adult subjects; Part 2 is to evaluate the pharmacokinetics of a single 1500 mg dose and two 3000 mg doses of gepotidacin given at a dosing interval (to be determined based on the pharmacokinetic and safety results from Part 1) in adolescent subjects. The duration of Part A will be approximately 47 days and 52 days for Part 2.
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Time of the Last Quantifiable Concentration (AUC[0-t]) After Single Dose Administration of Gepotidacin 1500 mg |
19.69 | — |
| PRIMARY Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) Extrapolated to Infinite Time (AUC[0-infinity]) After Single Dose Administration of Gepotidacin 1500 mg |
20.15 | — |
| PRIMARY Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to 24 Hours Post-dose (AUC[0-24]) After Single Dose Administration of Gepotidacin 1500 mg |
18.66 | — |
| PRIMARY Part 1- Period 1: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to 48 Hours Post-dose (AUC[0-48]) After Single Dose Administration of Gepotidacin 1500 mg |
19.72 | — |
| PRIMARY Part 1- Period 1: Maximum Observed Concentration (Cmax) After Single Dose Administration of Gepotidacin 1500 mg |
3.574 | — |
| PRIMARY Part 1- Period 2: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval |
91.21 | — |
| PRIMARY Part 1- Period 3: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval |
87.09 | — |
| PRIMARY Part 1- Period 2: Area Under the Concentration-time Curve From Time 0 (Pre-dose) to Time Tau (Tau=12) (AUC[0-tau]) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval |
38.15; 44.41 | — |
| PRIMARY Part 1- Period 3: AUC(0-tau) (Tau=6) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval |
24.09; 40.13 | — |
| PRIMARY Part 1- Period 2: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval |
83.45 | — |
| PRIMARY Part 1- Period 3: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval |
82.43 | — |
| PRIMARY Part 1- Period 2: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval |
90.53 | — |
| PRIMARY Part 1- Period 3: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval |
86.49 | — |
| PRIMARY Part 1- Period 2: Accumulation Ratio for Cmax (RoCmax) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval |
1.109 | — |
| PRIMARY Part 1- Period 2: Accumulation Ratio for AUC (RoAUC) Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval |
1.164 | — |
| PRIMARY Part 1- Period 3: RoCmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval |
1.544 | — |
| PRIMARY Part 1- Period 3: RoAUC Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval |
1.666 | — |
| PRIMARY Part 1- Period 2: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 12 Hour Dosing Interval |
9.937; 11.02 | — |
| PRIMARY Part 1- Period 3: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Dosing Interval |
8.423; 13.01 | — |
| PRIMARY Part 2- Period 1: AUC(0-t) After Single Dose Administration of Gepotidacin 1500 mg |
23.27 | — |
| PRIMARY Part 2- Period 1: AUC(0-infinity) After Single Dose Administration of Gepotidacin 1500 mg |
23.79 | — |
| PRIMARY Part 2- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg |
22.06 | — |
| PRIMARY Part 2- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg |
23.27 | — |
| PRIMARY Part 2- Period 1: Cmax After Single Dose Administration of Gepotidacin 1500 mg |
4.523 | — |
| PRIMARY Part 2- Period 2: AUC(0-t) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval |
115.6 | — |
| PRIMARY Part 2- Period 2: AUC(0-tau) (Tau=6) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval |
32.37; 53.85 | — |
| PRIMARY Part 2- Period 2: AUC(0-24) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval |
111.4 | — |
| PRIMARY Part 2- Period 2: AUC(0-48) Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval |
115.6 | — |
| PRIMARY Part 2- Period 2: Cmax Following Two Doses of Gepotidacin 3000 mg Administered at 6 Hour Interval |
10.86; 14.29 | — |
| PRIMARY Part 1: Number of Participants With Non-serious Adverse Events (AEs) and Serious Adverse Events (SAEs) |
0; 1; 10; 9; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Non-serious AEs and SAEs |
2; 9; 12; 0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Hematology Toxicities of Grade 3 or Higher |
0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Hematology Toxicities of Grade 3 or Higher |
0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Clinical Chemistry Toxicities of Grade 3 or Higher |
0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Clinical Chemistry Toxicities of Grade 3 or Higher |
1; 1; 3 | — |
| PRIMARY Part 1: Number of Participants With Urinalysis Toxicities of Grade 3 or Higher |
0; 0; 0; 0 | — |
| PRIMARY Part 2: Number of Participants With Urinalysis Toxicities of Grade 3 or Higher |
0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Systolic Blood Pressure (SBP) and Diastolic Blood Pressure (DBP) of Potential Clinical Importance |
0; 0; 1; 1 | — |
| PRIMARY Part 2: Number of Participants With SBP and DBP of Potential Clinical Importance |
0; 0; 0 | — |
| PRIMARY Part 1: Number of Participants With Abnormal Heart Rate of Potential Clinical Importance |
0; 0; 0; 1 | — |
| PRIMARY Part 2: Number of Participants With Abnormal Heart Rate of Potential Clinical Importance |
0; 1; 0 | — |
| PRIMARY Part 1: Period 1: Number of Participants With Abnormal 12-lead Electrocardiogram (ECG) Findings |
1; 8; 0; 0; 1; 11 | — |
| PRIMARY Part 1: Period 2: Number of Participants With Abnormal 12-lead ECG Findings |
2; 8; 0; 0; 2; 8 | — |
| PRIMARY Part 1: Period 3: Number of Participants With Abnormal 12-lead ECG Findings |
1; 11; 0; 0; 0; 9 | — |
| PRIMARY Part 2: Period 1: Number of Participants With Abnormal 12-lead ECG Findings |
1; 4; 0; 0; 0; 5 | — |
| PRIMARY Part 2: Period 2: Number of Participants With Abnormal 12-lead ECG Findings |
1; 6; 0; 0; 1; 7 | — |
| SECONDARY Part 1- Period 1: Total Unchanged Drug (Ae Total) After Single Dose Administration of Gepotidacin 1500 mg |
328.1 | — |
| SECONDARY Part 1- Period 1: Amount of Drug Excreted in Urine in a Time Interval (Ae[t1-t2]) After Single Dose Administration of Gepotidacin 1500 mg |
50.87; 92.98; 68.14; 47.68; 35.71; 29.10 | — |
| SECONDARY Part 1- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg (Urine) |
3340.0 | — |
| SECONDARY Part 1- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg (Urine) |
3567.9 | — |
| SECONDARY Part 1- Period 1: Percentage of the Given Dose of Drug Excreted in Urine (fe%) After Single Dose Administration of Gepotidacin 1500 mg |
21.874 | — |
| SECONDARY Part 1- Period 1: Renal Clearance of Drug (CLr) After Single Dose Administration of Gepotidacin 1500 mg |
16.66 | — |
| SECONDARY Part 1- Period 2: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval |
1452.7 | — |
| SECONDARY Part 1- Period 3: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval |
1293.9 | — |
| SECONDARY Part 1- Period 2: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval |
158.5; 186.1; 143.6; 66.80; 64.98; 204.1 | — |
| SECONDARY Part 1- Period 3: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval |
97.51; 216.8; 172.2; 242.3; 251.0; 151.6 | — |
| SECONDARY Part 1- Period 2: AUC(0-tau) (Tau=12 Hours Post-dose) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval (Urine) |
7287.4 | — |
| SECONDARY Part 1- Period 3: AUC(0-tau) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine) |
3943.5 | — |
| SECONDARY Part 1- Period 2: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval (Urine) |
17431.6 | — |
| SECONDARY Part 1- Period 3: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine) |
13174.1 | — |
| SECONDARY Part 1- Period 2: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval (Urine) |
19128.3 | — |
| SECONDARY Part 1- Period 3: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval (Urine) |
14277.1 | — |
| SECONDARY Part 1- Period 2: fe% After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval |
24.212 | — |
| SECONDARY Part 1- Period 3: fe% After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval |
21.565 | — |
| SECONDARY Part 1- Period 2: CLr After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval |
15.88 | — |
| SECONDARY Part 1- Period 3: CLr After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval |
14.81 | — |
| SECONDARY Part 2- Period 1: Ae Total After Single Dose Administration of Gepotidacin 1500 mg |
361.5 | — |
| SECONDARY Part 2- Period 1: Ae(t1-t2) After Single Dose Administration of Gepotidacin 1500 mg |
16.00; 130.5; 85.47; 58.74; 40.15; 30.87 | — |
| SECONDARY Part 2- Period 1: AUC(0-24) After Single Dose Administration of Gepotidacin 1500 mg (Urine) |
4513.7 | — |
| SECONDARY Part 2- Period 1: AUC(0-48) After Single Dose Administration of Gepotidacin 1500 mg (Urine) |
4948.4 | — |
| SECONDARY Part 2- Period 1: fe% After Single Dose Administration of Gepotidacin 1500 mg |
24.100 | — |
| SECONDARY Part 2- Period 1: CLr After Single Dose Administration of Gepotidacin 1500 mg |
15.56 | — |
| SECONDARY Part 2- Period 2: Ae Total After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval |
1719.4 | — |
| SECONDARY Part 2- Period 2: Ae(t1-t2) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval |
105.3; 202.0; 229.7; 244.9; 446.6; 228.3 | — |
| SECONDARY Part 2- Period 2: AUC(0-tau) (Tau=6 Hours Post-dose) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval (Urine) |
5364.4 | — |
| SECONDARY Part 2- Period 2: AUC(0-24) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval (Urine) |
22052.8 | — |
| SECONDARY Part 2- Period 2: AUC(0-48) After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval (Urine) |
24500.7 | — |
| SECONDARY Part 2- Period 2: fe% After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval |
28.657 | — |
| SECONDARY Part 2- Period 2: CLr After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval |
14.93 | — |
| SECONDARY Part 1- Period 1: Time to Reach Maximum Observed Plasma Concentration (Tmax) After Single Dose Administration of Gepotidacin 1500 mg |
3.000 | — |
| SECONDARY Part 1- Period 1: Lag Time Before Observation of Drug Concentrations in Sampled Matrix (Tlag) After Single Dose Administration of Gepotidacin 1500 mg |
0.000 | — |
| SECONDARY Part 1- Period 1: Terminal Phase Half-life (t1/2) After Single Dose Administration of Gepotidacin 1500 mg |
11.533 | — |
| SECONDARY Part 1- Period 2: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval |
2.000; 1.567 | — |
| SECONDARY Part 1- Period 3: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval |
2.633; 1.500 | — |
| SECONDARY Part 1- Period 2: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval |
0.000 | — |
| SECONDARY Part 1- Period 3: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval |
0.000 | — |
| SECONDARY Part 1- Period 2: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 12 Hour Dosing Interval |
10.976 | — |
| SECONDARY Part 1- Period 3: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Dosing Interval |
12.020 | — |
| SECONDARY Part 2- Period 1: Tmax After Single Dose Administration of Gepotidacin 1500 mg |
3.000 | — |
| SECONDARY Part 2- Period 1: Tlag After Single Dose Administration of Gepotidacin 1500 mg |
0.500 | — |
| SECONDARY Part 2- Period 1: t1/2 After Single Dose Administration of Gepotidacin 1500 mg |
12.984 | — |
| SECONDARY Part 2- Period 2: Tmax After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval |
2.750; 1.500 | — |
| SECONDARY Part 2- Period 2: Tlag After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval |
0.000 | — |
| SECONDARY Part 2- Period 2: t1/2 After Two Doses Administration of Gepotidacin 3000 mg at 6 Hour Interval |
6.982 | — |
Eligibility Criteria
Inclusion Criteria
- Subjects in Part 1 must be >=18 to =12 to =40 kilogram (kg) and body mass index (BMI) within the range 18.5 - 32.0 kg per square meter (inclusive).
- Male and/or female.
- Female subjects: A female subject is eligible to participate if she is not pregnant or breastfeeding, and at least one of the following conditions applies: a) Is not a woman of childbearing potential (WOCBP), or b) Is a WOCBP and using a contraceptive method that is highly effective, with a failure rate of 1.5 * upper limit of normal (ULN).
- Bilirubin >1.5 * ULN (isolated bilirubin >1.5 * 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.
- Urinary cotinine level indicative of smoking or history or regular use of tobacco- or nicotine-containing products within 3 months before screening.
- Clinically significant abnormal findings in serum chemistry, hematology, or urinalysis results obtained at screening or Day -1.
- Baseline corrected QT interval using the Fridericia formula (QTcF) of >450 msec.
- Subject 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.
- Subject is unable to comply with all study procedures, in the opinion of the investigator.
- Subject should not participate in the study, in the opinion of the investigator or sponsor.
Data sourced from ClinicalTrials.gov (NCT04079790). 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. Informational only — not medical advice.