Trial Outcomes & Findings for Dose-Escalation Safety and Pharmacokinetic Study of K305 (NCT NCT01304316)
NCT ID: NCT01304316
Last Updated: 2017-08-31
Results Overview
Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
COMPLETED
PHASE2
12 participants
Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutes
2017-08-31
Participant Flow
Participant milestones
| Measure |
Kovacaine Nasal Spray
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Overall Study
STARTED
|
12
|
|
Overall Study
COMPLETED
|
12
|
|
Overall Study
NOT COMPLETED
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Dose-Escalation Safety and Pharmacokinetic Study of K305
Baseline characteristics by cohort
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Age, Continuous
|
30.2 years
STANDARD_DEVIATION 7.45 • n=99 Participants
|
|
Sex: Female, Male
Female
|
6 Participants
n=99 Participants
|
|
Sex: Female, Male
Male
|
6 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
1 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
11 Participants
n=99 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Black or African American
|
1 Participants
n=99 Participants
|
|
Race (NIH/OMB)
White
|
10 Participants
n=99 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
PRIMARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesPopulation: Only 11 subjects in the 0.3 mg dose group had sufficient concentration levels to calculate Cmax.
Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Outcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Cmax of Oxymetazoline
0.3 mg
|
1.45 ng/mL
Standard Deviation 0.473
|
|
Cmax of Oxymetazoline
0.6 mg
|
2.05 ng/mL
Standard Deviation 0.748
|
PRIMARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesPopulation: Only 4 subjects in the 18 mg dose group and 7 subjects in the 36 mg dose group had sufficient concentration levels to calculate Cmax.
Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Outcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Cmax of Tetracaine
18 mg
|
0.243 ng/mL
Standard Deviation 0.113
|
|
Cmax of Tetracaine
36 mg
|
1.15 ng/mL
Standard Deviation 2.45
|
PRIMARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesExtra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Outcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Cmax of PBBA
Standard Dose
|
492 ng/mL
Standard Deviation 189
|
|
Cmax of PBBA
High Dose
|
886 ng/mL
Standard Deviation 289
|
PRIMARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesPopulation: Only 7 subjects in the 0.3 mg dose group and 0.6 mg dose group had sufficient concentration levels to calculate the half life.
Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Outcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Half Life of Oxymetazoline
0.3 mg
|
2.32 h
Standard Deviation 0.86
|
|
Half Life of Oxymetazoline
0.6 mg
|
1.72 h
Standard Deviation 0.46
|
PRIMARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesPopulation: An insufficient number of tetracaine plasma concentrations existed in each subject to determine a half life for tetracaine
Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesPopulation: Only 8 subjects in the standard dose group and 11 subjects in the high dose group had sufficient concentration levels to calculate Cmax.
Extra-vascular, non-compartmental analysis is used to derive pharmacokinetic parameters; estimated from observed plasma concentration values, the dose administered, the AUCs, and the terminal elimination phase rate constant for each dose group
Outcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Half Life of PBBA
Standard dose
|
1.00 h
Standard Deviation 0.33
|
|
Half Life of PBBA
High dose
|
1.01 h
Standard Deviation 0.32
|
SECONDARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesOutcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Pulse Oximetry Maximum Change From Baseline
Standard K305 Dose
|
0.9 % oxygen
Standard Deviation 0.9
|
|
Pulse Oximetry Maximum Change From Baseline
High K305 Dose
|
0.3 % oxygen
Standard Deviation 0.65
|
SECONDARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesOutcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Diastolic BP Maximum Change From Baseline
Standard K305 Dose
|
10.8 mmHg
Standard Deviation 7.74
|
|
Diastolic BP Maximum Change From Baseline
High K305 Dose
|
11.7 mmHg
Standard Deviation 8.28
|
SECONDARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesOutcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Systolic BP Maximum Change From Baseline
Standard K305 Dose
|
10.7 mmHg
Standard Deviation 7.67
|
|
Systolic BP Maximum Change From Baseline
High K305 Dose
|
14.7 mmHg
Standard Deviation 8.60
|
SECONDARY outcome
Timeframe: Baseline, 5, 10, 15, 20, 25, 30, 40, 50, 60, 70, 80, 90, 100, 110, 120 minutesOutcome measures
| Measure |
Kovacaine Nasal Spray
n=12 Participants
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl followed by 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: Tetracaine HCl 3% and Oxymetazoline HCl 0.05%
|
|---|---|
|
Pulse Rate Maximum Change From Baseline
Standard K305 Dose
|
5.2 bpm
Standard Deviation 4.39
|
|
Pulse Rate Maximum Change From Baseline
High K305 Dose
|
8.5 bpm
Standard Deviation 8.25
|
Adverse Events
Standard K305 Dose
High K305 Dose
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Standard K305 Dose
n=12 participants at risk
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 6 sprays of 0.1 mL - total of 18 mg tetracaine HCl and 0.3 mg oxymetazoline HCl
|
High K305 Dose
n=12 participants at risk
Tetracaine HCl 3% and Oxymetazoline HCl 0.05%: 12 sprays of 0.1 mL - total of 36 mg tetracaine HCl and 0.6 mg oxymetazoline HCl
|
|---|---|---|
|
Ear and labyrinth disorders
Tinnitus
|
0.00%
0/12 • 2 to 3 weeks
|
8.3%
1/12 • 2 to 3 weeks
|
|
Gastrointestinal disorders
Nausea
|
0.00%
0/12 • 2 to 3 weeks
|
8.3%
1/12 • 2 to 3 weeks
|
|
Gastrointestinal disorders
Vomiting
|
0.00%
0/12 • 2 to 3 weeks
|
8.3%
1/12 • 2 to 3 weeks
|
|
Injury, poisoning and procedural complications
Laceration
|
0.00%
0/12 • 2 to 3 weeks
|
8.3%
1/12 • 2 to 3 weeks
|
|
Investigations
Blood pressure diastolic increased
|
8.3%
1/12 • 2 to 3 weeks
|
0.00%
0/12 • 2 to 3 weeks
|
|
Investigations
Blood pressure increased
|
0.00%
0/12 • 2 to 3 weeks
|
8.3%
1/12 • 2 to 3 weeks
|
|
Nervous system disorders
Headache
|
25.0%
3/12 • 2 to 3 weeks
|
25.0%
3/12 • 2 to 3 weeks
|
|
Nervous system disorders
Sinus headache
|
8.3%
1/12 • 2 to 3 weeks
|
0.00%
0/12 • 2 to 3 weeks
|
|
Psychiatric disorders
Euphoric mood
|
0.00%
0/12 • 2 to 3 weeks
|
8.3%
1/12 • 2 to 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Epistaxis
|
16.7%
2/12 • 2 to 3 weeks
|
8.3%
1/12 • 2 to 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal congestion
|
41.7%
5/12 • 2 to 3 weeks
|
75.0%
9/12 • 2 to 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal discomfort
|
0.00%
0/12 • 2 to 3 weeks
|
33.3%
4/12 • 2 to 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Nasal dryness
|
8.3%
1/12 • 2 to 3 weeks
|
0.00%
0/12 • 2 to 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Oropharyngeal pain
|
8.3%
1/12 • 2 to 3 weeks
|
0.00%
0/12 • 2 to 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Rhinorrhoea
|
50.0%
6/12 • 2 to 3 weeks
|
75.0%
9/12 • 2 to 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Throat irritation
|
0.00%
0/12 • 2 to 3 weeks
|
16.7%
2/12 • 2 to 3 weeks
|
|
Respiratory, thoracic and mediastinal disorders
Upper-airway cough syndrome
|
0.00%
0/12 • 2 to 3 weeks
|
16.7%
2/12 • 2 to 3 weeks
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place