Trial Outcomes & Findings for Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis (NCT NCT05225805)
NCT ID: NCT05225805
Last Updated: 2024-06-17
Results Overview
Appropriate non-compartmental techniques were used to obtain estimates for the PK parameter Tmax in plasma for lefamulin and its metabolite BC-8041. Time to reach maximum plasma concentration of lefamulin following drug administration (Tmax) Tmax will be determined by direct inspection of the concentration versus time data by WinNonlin.
Recruitment status
COMPLETED
Study phase
PHASE1
Target enrollment
13 participants
Primary outcome timeframe
Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dose
Results posted on
2024-06-17
Participant Flow
This study was conducted at multiple investigative sites in United States.
A total of 13 subjects (4 females, 9 males) was enrolled in the study and treated in the study NAB-BC-3781-1014. One subject failed screening.
Participant milestones
| Measure |
Group A (IV-Oral)
Group A will receive single dose of lefamulin 150 mg IV infusion in 250 mL citrate buffered saline over 1 hour followed by lefamulin 600-mg immediate-release (IR) tablet orally in the fasted state.
Lefamulin: Antibiotic
|
Group B (Oral-IV)
Group B will receive single dose of lefamulin 600 mg immediate-release (IR) tablet orally in the fasted state followed by single dose of lefamulin 150 mg IV infusion in 250 mL citrate buffered saline over 1 hour.
Lefamulin: Antibiotic
|
|---|---|---|
|
Overall Study
STARTED
|
6
|
7
|
|
Overall Study
COMPLETED
|
6
|
7
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Study to Assess the Safety and PK of Oral and IV Xenleta in Adults With Cystic Fibrosis
Baseline characteristics by cohort
| Measure |
Group A (IV-Oral)
n=6 Participants
Group A will receive single dose of lefamulin 150 mg IV infusion in 250 mL citrate buffered saline over 1 hour followed by lefamulin 600-mg immediate-release (IR) tablet orally in the fasted state.
Lefamulin: Antibiotic
|
Group B (Oral-IV)
n=7 Participants
Group B will receive single dose of lefamulin 600 mg immediate-release (IR) tablet orally in the fasted state followed by single dose of lefamulin 150 mg IV infusion in 250 mL citrate buffered saline over 1 hour.
Lefamulin: Antibiotic
|
Total
n=13 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
27.0 Years
STANDARD_DEVIATION 11.14 • n=99 Participants
|
31.1 Years
STANDARD_DEVIATION 9.01 • n=107 Participants
|
29.2 Years
STANDARD_DEVIATION 9.84 • n=206 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=99 Participants
|
3 Participants
n=107 Participants
|
4 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
5 Participants
n=99 Participants
|
4 Participants
n=107 Participants
|
9 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
6 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
6 Participants
n=99 Participants
|
7 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dosePopulation: Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.
Appropriate non-compartmental techniques were used to obtain estimates for the PK parameter Tmax in plasma for lefamulin and its metabolite BC-8041. Time to reach maximum plasma concentration of lefamulin following drug administration (Tmax) Tmax will be determined by direct inspection of the concentration versus time data by WinNonlin.
Outcome measures
| Measure |
Lefamulin Oral Treatment
n=13 Participants
Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.
|
Lefamulin IV Treatment
n=13 Participants
Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.
|
|---|---|---|
|
The Median for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Tmax in Cystic Fibrosis (CF) Patients.
Lefamulin
|
2.00 hours
Interval 0.983 to 3.9
|
0.583 hours
Interval 0.5 to 1.717
|
|
The Median for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Tmax in Cystic Fibrosis (CF) Patients.
Lefamulin metabolite BC-8041
|
1.517 hours
Interval 1.017 to 4.017
|
1.500 hours
Interval 0.933 to 1.817
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dosePopulation: Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.
Appropriate non-compartmental techniques will be used to obtain estimates for the PK parameter Cmax in plasma for lefamulin and its metabolite BC-8041. Maximum observed plasma concentration (Cmax) Cmax was determined by direct inspection of the concentration versus time data by WinNonlin.
Outcome measures
| Measure |
Lefamulin Oral Treatment
n=13 Participants
Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.
|
Lefamulin IV Treatment
n=13 Participants
Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.
|
|---|---|---|
|
The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Cmax in CF Patients.
Lefamulin
|
1.314 mg/L
Geometric Coefficient of Variation 0.308
|
1.924 mg/L
Geometric Coefficient of Variation 0.417
|
|
The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter Cmax in CF Patients.
Lefamulin Metabolite BC-8041
|
0.351 mg/L
Geometric Coefficient of Variation 0.417
|
0.030 mg/L
Geometric Coefficient of Variation 0.470
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dosePopulation: Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.
Appropriate non-compartmental techniques will be used to obtain estimates for the PK parameter (AUC0-last) in plasma for lefamulin and its metabolite BC-8041. AUC calculations will be performed using the linear/log trapezoidal rule. AUC0-last will be calculated between t0hr and the last measurable concentration. Area under the drug concentration curve from time zero (0 h) to 24 h (AUC0-last)
Outcome measures
| Measure |
Lefamulin Oral Treatment
n=13 Participants
Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.
|
Lefamulin IV Treatment
n=13 Participants
Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.
|
|---|---|---|
|
The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-last) in CF Patients.
Lefamulin
|
6.881 mg·h/L
Geometric Coefficient of Variation 0.380
|
6.220 mg·h/L
Geometric Coefficient of Variation 0.286
|
|
The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-last) in CF Patients.
Lefamulin Metabolite BC-8041
|
1.990 mg·h/L
Geometric Coefficient of Variation 0.442
|
0.232 mg·h/L
Geometric Coefficient of Variation 0.536
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dosePopulation: Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.
Appropriate non-compartmental techniques will be used to obtain estimates for PK parameter AUC(0-inf) in plasma for lefamulin and its metabolite BC-8041. AUC calculations will be performed using the linear/log trapezoidal rule. AUC(0-inf) will be will be calculated between t0hr and infinity. Area under the drug concentration curve from time zero (0 h) to infinity (AUC(0-inf)
Outcome measures
| Measure |
Lefamulin Oral Treatment
n=13 Participants
Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.
|
Lefamulin IV Treatment
n=13 Participants
Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.
|
|---|---|---|
|
The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-inf) in CF Patients.
Lefamulin
|
7.277 mg·h/L
Geometric Coefficient of Variation 0.384
|
6.568 mg·h/L
Geometric Coefficient of Variation 0.286
|
|
The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter AUC(0-inf) in CF Patients.
Metabolite BC-8041
|
2.095 mg·h/L
Geometric Coefficient of Variation 0.448
|
0.272 mg·h/L
Geometric Coefficient of Variation 0.517
|
PRIMARY outcome
Timeframe: Pre-dose, 0.5 hr, 1 hr, 1.5 hrs, 2 hrs, 4 hrs, 8 hrs, 12 hrs & 24 hrs Post-dosePopulation: Pharmacokinetic (PK) Population: All 13 adult subjects completed both periods of the study. Plasma samples from 13 subjects were analyzed for lefamulin and BC-8041.
Appropriate non-compartmental techniques will be used to obtain estimates for thr PK parameter t1/2 in plasma for lefamulin and its metabolite BC-8041. Apparent elimination half-life calculated as ln(2)/ke (t½)
Outcome measures
| Measure |
Lefamulin Oral Treatment
n=13 Participants
Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.
|
Lefamulin IV Treatment
n=13 Participants
Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.
|
|---|---|---|
|
The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter t1/2 in CF Patients.
Lefamulin
|
6.422 hours
Geometric Coefficient of Variation 0.182
|
6.297 hours
Geometric Coefficient of Variation 0.188
|
|
The Key Geometric Mean for Lefamulin and Its Main Metabolite BC-8041 for PK Plasma Parameter t1/2 in CF Patients.
Metabolite BC-8041
|
5.796 hours
Geometric Coefficient of Variation 0.175
|
8.128 hours
Geometric Coefficient of Variation 0.176
|
Adverse Events
Lefamulin Oral Treatment
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Lefamulin IV Treatment
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Total
Serious events: 0 serious events
Other events: 6 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Lefamulin Oral Treatment
n=13 participants at risk
Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.
|
Lefamulin IV Treatment
n=13 participants at risk
Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.
|
Total
n=13 participants at risk
Lefamulin oral treatment + Lefamulin IV treatment
Lefamulin as a 600-mg IR tablet. The oral treatment will be swallowed whole with 6 to 8 ounces of water at least 1 hour before or 2 hours after a meal.
Lefamulin 150 mg in 250 mL citrate buffered saline IV infusion over 1 hour.
|
|---|---|---|---|
|
Gastrointestinal disorders
Diarrhea
|
15.4%
2/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
0.00%
0/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
15.4%
2/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
|
Gastrointestinal disorders
Nausea
|
15.4%
2/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
15.4%
2/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
|
Gastrointestinal disorders
Vomiting
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
0.00%
0/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
|
General disorders
Infusion site erythema
|
0.00%
0/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
|
General disorders
Infusion site pain
|
0.00%
0/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
|
Congenital, familial and genetic disorders
Cystic fibrosis gastrointestinal disease
|
0.00%
0/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
|
Injury, poisoning and procedural complications
Tooth fracture
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
0.00%
0/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
|
Nervous system disorders
Presyncope
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
0.00%
0/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
7.7%
1/13 • Up-to Follow-up (4 to 7 days after the final dose).
Safety analysis set (SfAS): All subjects who receive any full or partial dose of lefamulin. The SfAS will be used for the analysis of safety data.
|
Additional Information
Christine Guico-Pabia, MD, MBA, MPH
Nabriva Therapeutics US, Inc.
Phone: 610-981-2874
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60