Clinical Trial Results:
Pharmacokinetics of subcutaneously given dexmedetomidine in healthy volunteers
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Summary
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EudraCT number |
2015-004698-34 |
Trial protocol |
FI |
Global end of trial date |
30 Nov 2017
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Results information
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Results version number |
v1(current) |
This version publication date |
25 Oct 2020
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First version publication date |
25 Oct 2020
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Other versions |
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Summary report(s) |
ScDex_journal_article |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
ScDex_v1.0
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
- | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Turku University Hospital
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Sponsor organisation address |
Kiinamyllynkatu 4-8, Turku, Finland, 20520
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Public contact |
Department of Anesthesiology and In, University Of Turku, teijo.saari@utu.fi
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Scientific contact |
Department of Anesthesiology and In, University Of Turku, teijo.saari@utu.fi
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
30 Nov 2017
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
31 May 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
30 Nov 2017
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The aim of this study is to investigate the pharmacokinetics of subcutaneously administered dexmedetomidine in healthy volunteers. The absolute bioavailability of subcutaneously administered dexmedetomidine will be calculated.
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Protection of trial subjects |
Heart rate, intra-arterial blood pressure, and peripheral oxygen saturation were monitored throughout the clinical phase of the study (18 hours after dexmedetomidine dosing). The local tolerability of dexmedetomidine was assessed by the study participants and by visual inspection by the investigator immediately prior to drug administration (baseline) and at 1, 5, and 10 h. Subjects were instructed to inform the researchers any drug-related effects. Possible local dermal irritation, inflammation, bleeding, and swelling were monitored 18 hours after dexmedetomidine dosing.
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Background therapy |
None | ||
Evidence for comparator |
NA | ||
Actual start date of recruitment |
01 Feb 2016
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Finland: 10
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Worldwide total number of subjects |
10
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EEA total number of subjects |
10
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
10
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From 65 to 84 years |
0
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85 years and over |
0
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Recruitment
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Recruitment details |
- | ||||||||||||||||||
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Pre-assignment
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Screening details |
- | ||||||||||||||||||
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Pre-assignment period milestones
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Number of subjects started |
10 | ||||||||||||||||||
Number of subjects completed |
10 | ||||||||||||||||||
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Period 1
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Period 1 title |
First period
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Is this the baseline period? |
Yes | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intravenous arm | ||||||||||||||||||
Arm description |
Subjects randomized to intravenous arm were administered 1-μg/kg doses of dexmedetomidine intravenously. Dexmedetomidine (Dexdor® 100 μg/ml, Orion Pharma, Espoo, Finland) were diluted in 0.9% saline solution (Natriumklorid B. Braun® 9 mg/ml, B. Braun, Melsungen, Germany) and administered at a concentration of 8 μg/ml during 10 min by infusion (Perfusor® Space Infusion Pump, B. Braun). | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
dexmedetomidine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1-μg/kg dose, administered intravenously at a concentration of 8 μg/ml during 10 min by continuous infusion
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Arm title
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Subcutaneous arm | ||||||||||||||||||
Arm description |
Subjects randomized to subcutaneous arm were administered 1-μg/kg doses of dexmedetomidine intravenously. Dexmedetomidine (Dexdor® 100 μg/ml) was diluted in 0.9% saline solution and administered at a concentration of 50 μg/ml during 10 min by continuous infusion (Perfusor® Space Infusion Pump, B. Braun). | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
dexmedetomidine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
1-μg/kg dose administered subcutaneously at a concentration of 50 μg/ml during 10 min by continuous infusion.
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Period 2
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Period 2 title |
Second period
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Is this the baseline period? |
No | ||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Not blinded | ||||||||||||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Intravenous arm | ||||||||||||||||||
Arm description |
Subjects randomized to intravenous arm were administered 1-μg/kg doses of dexmedetomidine intravenously. Dexmedetomidine (Dexdor® 100 μg/ml, Orion Pharma, Espoo, Finland) was diluted in 0.9% saline solution (Natriumklorid B. Braun® 9 mg/ml, B. Braun, Melsungen, Germany) and administered at a concentration of 8 μg/ml during 10 min by infusion (Perfusor® Space Infusion Pump, B. Braun). | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
dexmedetomidine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Intravenous use
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Dosage and administration details |
1-μg/kg dose, administered at a concentration of 8 μg/ml during 10 min by continuous infusion
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Arm title
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Subcutaneous arm | ||||||||||||||||||
Arm description |
Subjects randomized to subcutaneous arm were administered 1-μg/kg doses of dexmedetomidine intravenously. Dexmedetomidine (Dexdor® 100 μg/ml) was diluted in 0.9% saline solution and administered at a concentration of 50 μg/ml during 10 min by continuous infusion (Perfusor® Space Infusion Pump, B. Braun) | ||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||
Investigational medicinal product name |
dexmedetomidine
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Infusion
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Routes of administration |
Subcutaneous use
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Dosage and administration details |
1-μg/kg dose administered at a concentration of 50 μg/ml during 10 min by continuous infusion.
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Baseline characteristics reporting groups
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Reporting group title |
First period
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Subject analysis sets
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Subject analysis set title |
Pharmacokinetics
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Subject analysis set type |
Full analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Data were log-transformed before statistical analysis, but nontransformed results are reported. The peak plasma concentrations and corresponding peak plasma concentration times were observed directly from the data. For each subject, the terminal log-linear phase of the plasma dexmedetomidine concentration-time curve was identified visually, and the elimination rate constant was determined by regression analysis on the basis of at least four time points. The elimination half-life was then calculated from the equation t1/2 = ln 2 / kel. The area under the dexmedetomidine plasma concentration-time curve was calculated using the trapezoidal method, with the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Apparent clearance and apparent volume of distribution of dexmedetomidine during the elimination phase were also calculated, with noncompartmental methods based on statistical moment theory.
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Subject analysis set title |
Pharmacodynamics
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Subject analysis set type |
Intention-to-treat | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
Heart rate, intra-arterial blood pressure, and peripheral oxygen saturation were recorded at times of blood sampling (immediately prior to administration of dexmedetomidine (baseline) and thereafter at 5, 10, 15, 30, and 45 min and 1, 1.5, 2, 3, 5, 8, and 10 h after the start of dexmedetomidine administration). At the same time points, also psychomotor drug effects on vigilance and performance were assessed with visual analog scales (VAS). Subjective assessments (alert to drowsy, very good performance to very poor performance) were recorded with 100-mm horizontal VAS lines. For each pharmacodynamic variable, the AUC was determined using the trapezoidal rule.
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Subject analysis set title |
Local tolerability
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Subject analysis set type |
Safety analysis | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Subject analysis set description |
The local tolerability of SC and IV administered dexmedetomidine was assessed with VAS scores by the study participants and by visual inspection by the investigator immediately prior to drug administration (baseline) and at 1, 5, and 10 h. Subjective effects (no local pain/strong pain, no irritation/strong irritation, no pruritus/strong pruritus, no numbness/total numbness) were recorded. In the visual inspection by the investigator, possible local dermal irritation, inflammation, bleeding, and swelling were recorded. For each assessment, the AUC was calculated using the trapezoidal rule.
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End points reporting groups
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Reporting group title |
Intravenous arm
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Reporting group description |
Subjects randomized to intravenous arm were administered 1-μg/kg doses of dexmedetomidine intravenously. Dexmedetomidine (Dexdor® 100 μg/ml, Orion Pharma, Espoo, Finland) were diluted in 0.9% saline solution (Natriumklorid B. Braun® 9 mg/ml, B. Braun, Melsungen, Germany) and administered at a concentration of 8 μg/ml during 10 min by infusion (Perfusor® Space Infusion Pump, B. Braun). | ||
Reporting group title |
Subcutaneous arm
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Reporting group description |
Subjects randomized to subcutaneous arm were administered 1-μg/kg doses of dexmedetomidine intravenously. Dexmedetomidine (Dexdor® 100 μg/ml) was diluted in 0.9% saline solution and administered at a concentration of 50 μg/ml during 10 min by continuous infusion (Perfusor® Space Infusion Pump, B. Braun). | ||
Reporting group title |
Intravenous arm
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Reporting group description |
Subjects randomized to intravenous arm were administered 1-μg/kg doses of dexmedetomidine intravenously. Dexmedetomidine (Dexdor® 100 μg/ml, Orion Pharma, Espoo, Finland) was diluted in 0.9% saline solution (Natriumklorid B. Braun® 9 mg/ml, B. Braun, Melsungen, Germany) and administered at a concentration of 8 μg/ml during 10 min by infusion (Perfusor® Space Infusion Pump, B. Braun). | ||
Reporting group title |
Subcutaneous arm
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Reporting group description |
Subjects randomized to subcutaneous arm were administered 1-μg/kg doses of dexmedetomidine intravenously. Dexmedetomidine (Dexdor® 100 μg/ml) was diluted in 0.9% saline solution and administered at a concentration of 50 μg/ml during 10 min by continuous infusion (Perfusor® Space Infusion Pump, B. Braun) | ||
Subject analysis set title |
Pharmacokinetics
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Data were log-transformed before statistical analysis, but nontransformed results are reported. The peak plasma concentrations and corresponding peak plasma concentration times were observed directly from the data. For each subject, the terminal log-linear phase of the plasma dexmedetomidine concentration-time curve was identified visually, and the elimination rate constant was determined by regression analysis on the basis of at least four time points. The elimination half-life was then calculated from the equation t1/2 = ln 2 / kel. The area under the dexmedetomidine plasma concentration-time curve was calculated using the trapezoidal method, with the linear trapezoidal rule for increasing concentrations and the logarithmic trapezoidal rule for decreasing concentrations. Apparent clearance and apparent volume of distribution of dexmedetomidine during the elimination phase were also calculated, with noncompartmental methods based on statistical moment theory.
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Subject analysis set title |
Pharmacodynamics
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Subject analysis set type |
Intention-to-treat | ||
Subject analysis set description |
Heart rate, intra-arterial blood pressure, and peripheral oxygen saturation were recorded at times of blood sampling (immediately prior to administration of dexmedetomidine (baseline) and thereafter at 5, 10, 15, 30, and 45 min and 1, 1.5, 2, 3, 5, 8, and 10 h after the start of dexmedetomidine administration). At the same time points, also psychomotor drug effects on vigilance and performance were assessed with visual analog scales (VAS). Subjective assessments (alert to drowsy, very good performance to very poor performance) were recorded with 100-mm horizontal VAS lines. For each pharmacodynamic variable, the AUC was determined using the trapezoidal rule.
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Subject analysis set title |
Local tolerability
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Subject analysis set type |
Safety analysis | ||
Subject analysis set description |
The local tolerability of SC and IV administered dexmedetomidine was assessed with VAS scores by the study participants and by visual inspection by the investigator immediately prior to drug administration (baseline) and at 1, 5, and 10 h. Subjective effects (no local pain/strong pain, no irritation/strong irritation, no pruritus/strong pruritus, no numbness/total numbness) were recorded. In the visual inspection by the investigator, possible local dermal irritation, inflammation, bleeding, and swelling were recorded. For each assessment, the AUC was calculated using the trapezoidal rule.
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End point title |
Bioavailability | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
0-10 hours
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Statistical analysis title |
Comparison of pharmacokinetic parameters | ||||||||||||||||||||||||
Comparison groups |
Intravenous arm v Intravenous arm v Subcutaneous arm v Subcutaneous arm
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Number of subjects included in analysis |
18
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||||||
Method |
Kruskal-wallis | ||||||||||||||||||||||||
Confidence interval |
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End point title |
Area under the plasma concentration-time curve | ||||||||||||||||||||||||
End point description |
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End point type |
Primary
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End point timeframe |
0-10 hours
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Statistical analysis title |
Comparison of pharmacokinetic parameters | ||||||||||||||||||||||||
Comparison groups |
Intravenous arm v Intravenous arm v Subcutaneous arm v Subcutaneous arm
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Number of subjects included in analysis |
18
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Analysis specification |
Pre-specified
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Analysis type |
other | ||||||||||||||||||||||||
P-value |
< 0.05 | ||||||||||||||||||||||||
Method |
Kruskal-wallis | ||||||||||||||||||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
0-10 hours
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Assessment type |
Systematic | |||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||
Dictionary version |
10
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Reporting groups
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Reporting group title |
Local tolerability
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Reporting group description |
- | |||||||||||||||||||||
Reporting group title |
Vital signs
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Reporting group description |
- | |||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 1% | ||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/29666901 |
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