Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12614000514606
Ethics application status
Approved
Date submitted
9/05/2014
Date registered
15/05/2014
Date last updated
11/02/2021
Date data sharing statement initially provided
11/02/2021
Date results provided
11/02/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
The pharmacokinetics of intranasal droperidol in healthy volunteers.
Scientific title
A randomised cross-over study comparing the pharmacokinetics of intranasal droperidol to 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.
Control group
Active

Outcomes
Primary outcome [1] 292081 0
To evaluate the pharmacokinetics of intranasal droperidol and to compare these with equivalent doses of 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
Sex
Males
Can healthy volunteers participate?
Yes
Key exclusion criteria
Female gender
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 both 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). 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 the subsequent visit, 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
Completed
Date of first participant enrolment
Anticipated
14/07/2014
Actual
15/12/2014
Date of last participant enrolment
Anticipated
16/01/2015
Actual
16/01/2015
Date of last data collection
Anticipated
Actual
1/04/2015
Sample size
Target
7
Accrual to date
Final
7
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
Country [1] 289203 0
Australia
Funding source category [2] 289204 0
Commercial sector/Industry
Name [2] 289204 0
Teleflex Medical
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
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
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
[email protected]
Contact person for public queries
Name 48235 0
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
[email protected]
Contact person for scientific queries
Name 48236 0
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
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
10616Study protocol    366294-(Uploaded-27-07-2020-10-26-30)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseThe pharmacokinetics of intranasal droperidol in volunteers characterised via population modelling.2018https://dx.doi.org/10.1177/2050312118813283
N.B. These documents automatically identified may not have been verified by the study sponsor.