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Trial registered on ANZCTR


Trial ID
ACTRN12614000514606
Ethics application status
Approved
Date submitted
9/05/2014
Date registered
15/05/2014
Date last updated
15/05/2014
Type of registration
Prospectively registered

Titles & IDs
Public title
The pharmacokinetics of intranasal droperidol in healthy volunteers.
Scientific title
A randomised three-way cross-over study comparing the pharmacokinetics of intranasal droperidol to intramuscular and intravenous droperidol in healthy volunteers:
Secondary ID [1] 284571 0
Nil Known
Universal Trial Number (UTN)
Trial acronym
INKDROP Study (IntraNasal pharmacoKinetics of DROPeridol)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Pharmacokinetics of intranasal drug delivery in healthy human volunteers. 291847 0
Condition category
Condition code
Other 292209 292209 0 0
Research that is not of generic health relevance and not applicable to specific health categories listed above

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intranasal administration of droperidol 0.02mg/kg as a single dose with 1 week wash out between study arms.
Intervention code [1] 289344 0
Treatment: Drugs
Comparator / control treatment
Intravenous droperidol 0.02mg/kg as a single dose.
Intramuscular droperidol 0.02mg/kg as a single dose
Control group
Active

Outcomes
Primary outcome [1] 292081 0
To evaluate the pharmacokinetics of intranasal droperidol and to compare these with equivalent doses of intramuscular and intravenous droperidol administered to healthy volunteers.

These will include peak serum droperidol concentration (Cmax), time to peak serum concentration (Tmax), terminal elimination half-life (t1/2), area under the time concentration curve (AUC).
Timepoint [1] 292081 0
Pharmacokinetic blood sampling at time 0, 15, 30, 60 minutes post-dosing and 2, 3, 4, 6, 8, 10 hours post-dosing.
Secondary outcome [1] 308178 0
Assess safety and tolerability of intranasal droperidol following a single low dose
Vital signs (blood pressure/heart rate/oxygen saturations/temperature)
Level of consciousness
Local adverse events: nasal irritation, bleeding, or any reported symptoms
Systemic adverse events
12-lead ECGs traces and QT-interval duration
Timepoint [1] 308178 0
Subjects observed for 12 hours post-dosing for each study arm.

Eligibility
Key inclusion criteria
Healthy adult males aged between 18 and 55 years
Body weight > 50kg and < 100 kg with BMI < 28
Minimum age
18 Years
Maximum age
55 Years
Gender
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Allergy to droperidol
Previous history of any dystonic reaction to medications
Abnormal nasal anatomy
Previous nasal surgery or nasal trauma that may interfere with administration of absorption of intranasal medication
Current or recent upper respiratory tract infection
Use of any prescription or non-prescription drugs that may affect droperidol metabolism or nasal physiology (vasoconstrictors e.g. phenylephrine) within the past seven days
Treatment with medication known to prolong the QT interval
Absolute QT calculated as the average of three limb lead and three chest lead (V2-V4) QT interval duration.
Abnormal 12-lead ECG on screening with QTcorrected> 480 msec using Sagie regression QTc calculation formula and correlated with Isbister QT-heart rate pair nomogram.
Any known cardiovascular, gastrointestinal, pulmonary, renal, haematologic or liver disease
Any psychiatric or mental health disorder or previous history of antipsychotic medication use

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Volunteers will be recruited by advertisement on Monash University research web site and by advertisement at Dandenong Hospital.

A target number of 7 participants (completing all three arms of the study) will be sought.

- Screening visit:
Potential participants will contact one of the study investigators and be asked to attend a screening visit, where the study protocol will be explained and any question answered. They will be asked questions regarding their general health and to confirm that meet the inclusion criteria, and have no exclusion criteria. If acceptable, written consent will be sought. Once consent is provided, participants will be allocated a study identification code and their eligibility for study randomization will be confirmed. They will be weighed and BMI will be calculated. A 12-lead ECG will be recorded and assessed for the presence of normal sinus rhythm, with normal conduction intervals and a normal QTc (< 480msec). A pregnancy test will apply for female participants. If they do not have any exclusion criteria, the participants will be eligible to remain in the study and will be randomized to a sequence of drug administration on three subsequent visits, at least one week apart.

Participants not completing the study will be replaced and given the same randomization order.

The route of droperidol administration will be randomized by random number generation and subjects allocated to a sequence at the time of enrolment from one of seven envelopes. Allocation will concealed from the enrolling investigator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Volunteers will be randomized by random number generation to the sequence of which route of droperidol administration will be first.

Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Crossover
Other design features
Phase
Phase 4
Type of endpoint(s)
Pharmacokinetics
Statistical methods / analysis
Serum drug concentration will be reported as mean +/- SD in ng/ml. Statistical comparisons of the primary pharmacokinetic parameters will be compared between groups using one-way ANOVA with Newman-Keuls post-test for parametric data and Dunnet’s post-test for non-parametric data.

Previous pharmacokinetic studies using droperidol intravenously have reported serum drug concentrations after doses of up to 0.15 mg/kg. This is significantly (ten-fold) higher than the dose we will be using in this study. We expect that after intravenous administration of droperidol at the proposed dose of 0.02 mg/kg peak serum concentration will be around 150 to 200 ng/ml (+/- SD 30-40 ng/ml). If these concentrations are achieved in this study, it would give an acceptable 95% confidence interval of +/- 25 ng/ml.

With regards to intranasal drug delivery of droperidol, the only comparable data available is from the haloperidol study by Miller et al, (2008). In this study, mean peak haloperidol concentration in four subjects post-intranasal administration were 1/3 of those seen intravenously with a standard deviation of +/- 20 ng/ml. For the proposed study, using the expected peak droperidol concentration assumption above for the IV group, a calculated sample size of n = 7 subjects in the IN and IV arms would result in an expected mean peak serum concentration of droperidol in the intranasal group of around 60 ng/ml with a 95% CI of +/- 15 ng/ml. (Confidence intervals and sample size calculated using STATA statistical software using binomial confidence intervals).

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 2447 0
Dandenong Hospital - Dandenong
Recruitment postcode(s) [1] 8066 0
3175 - Dandenong

Funding & Sponsors
Funding source category [1] 289203 0
Hospital
Name [1] 289203 0
Department of Emergency Medicine
Dandenong Hospital
Address [1] 289203 0
125 David Street
Dandenong, 3175
Victoria
Country [1] 289203 0
Australia
Funding source category [2] 289204 0
Commercial sector/Industry
Name [2] 289204 0
Teleflex Medical
Address [2] 289204 0
182-184 Stawell Street
Burnley , 3121
Victoria
Country [2] 289204 0
Australia
Primary sponsor type
Hospital
Name
Monash Health
Address
Department of Emergency Medicine
Dandenong Hospital
125 David Street
Dandenong, 3175, Vic
Country
Australia
Secondary sponsor category [1] 287880 0
None
Name [1] 287880 0
Address [1] 287880 0
Country [1] 287880 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290977 0
Monash Health Human Research and Ethic Committee A
Ethics committee address [1] 290977 0
Research Directorate
Monash Medical Centre
246 Clayton Rd
Clayton, 3168, Vic
Ethics committee country [1] 290977 0
Australia
Date submitted for ethics approval [1] 290977 0
14/04/2014
Approval date [1] 290977 0
01/05/2014
Ethics approval number [1] 290977 0
14127A

Summary
Brief summary
The intranasal (IN) route of drug administration has many advantages. It has the potential to eliminate the pain, anxiety, and distress that can be associated with the use of needles for IV or IMI drug delivery. The risk of needle-stick injury and blood-borne infection is also minimized by the use of needleless systems. In addition, drug administration can occur more quickly than intravenous administration as there is no need to spend time siting a cannula and there is reduced resource utilisation.

Recent observational research in the ED setting has revealed that more than 50% of inserted intravenous cannulae are never used for therapeutic purposes and pose a significant risk for skin infection and septicaemia if left in-situ.

There is currently no data examining the pharmacokinetic profile of intranasal droperidol. However, based upon results with intranasal haloperidol, it is likely that droperidol, having similar pharmacokinetic properties, may display a comparable intranasal absorption profile.

Currently, there are no anti-emetics or antipsychotic medications being administered intranasally in the clinical setting. As a result, if the pharmacokinetic profile is favourable, droperidol may be a useful drug to consider for clinical trials of intranasal treatment of acute behavioural disturbance and anti-emesis.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 48234 0
Prof Andis Graudins
Address 48234 0
Department of Emergency Medicine
Dandenong Hospital
125 David Street
Dandenong, Vic, 3175
Country 48234 0
Australia
Phone 48234 0
+61 3 9554 9340
Fax 48234 0
Email 48234 0
andis.graudins@monash.edu
Contact person for public queries
Name 48235 0
Prof Andis Graudins
Address 48235 0
Department of Emergency Medicine
Dandenong Hospital
125 David Street
Dandenong, Vic, 3175
Country 48235 0
Australia
Phone 48235 0
+61 3 9554 9340
Fax 48235 0
Email 48235 0
andis.graudins@monash.edu
Contact person for scientific queries
Name 48236 0
Prof Andis Graudins
Address 48236 0
Department of Emergency Medicine
Dandenong Hospital
125 David Street
Dandenong, Vic, 3175
Country 48236 0
Australia
Phone 48236 0
+61 3 9554 9340
Fax 48236 0
Email 48236 0
andis.graudins@monash.edu