Clinical trial NCT01363089: Study to Assess the PK of Ketorolac Tromethamine Intranasal and to Assess the Effects of a Oxymetazoline Hydrochloride on the PK of Ketorolac Tromethamine
Official title: Open Label, 2-Way Crossover Study to Assess the PK of Intranasal Ketorolac Tromethamine and to Assess the Effects of a Single Dose of Oxymetazoline Hydrochloride on the PK of Intranasal Ketorolac Tromethamine in Healthy Male Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Assess Pharmacokinetics of Ketorolac Tromethamine Intranasal and Assess Effects of a Oxymetazoline Hydrochloride on the PK of Ketorolac Tromethamine
Lead sponsor: Egalet Ltd
Sponsor class: INDUSTRY
First posted: 2011-06-01
Enrollment: 21
Sex: MALE
Minimum age (years): 18
Maximum age (years): 62
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: TREATMENT

Brief summary: This was an open label, two way crossover study in healthy male subjects. Two treatments were administered to each subject, one treatment per study period, in a randomized manner. Subjects remained resident in the Clinical Unit from the evening of Day 1 until the morning of Day 2 of each period and there was a washout period of at least 2 days between treatments. A post study medical examination was performed prior to discharge in Period 2.

The objective of this study was to assess the effects of a single dose of intranasal oxymetazoline hydrochloride on the pharmacokinetics of intranasal ketorolac in healthy male subjects.


Eligibility criteria: Inclusion Criteria:

* Subject was male and aged 18 to 62 years inclusive
* Male subjects with female partners of child bearing potential must have consented to use a medically acceptable method of contraception (oral or implanted contraceptive hormones, intrauterine device or surgical sterilization plus condom or diaphragm with spermicidal agent) throughout the study period
* Subject had given signed informed consent
* Subject was within 20% of normal weight for his height and body build according to the table of "Desirable Weights for Men and Women" (Metropolitan Life Insurance Co. 1999)
* Subject's medical history was considered normal, with no clinically significant abnormalities
* Subject was considered to be in good health in the opinion of the Investigator, as determined by a pre-study physical examination with no clinically significant abnormalities, vital signs within normal ranges and an electrocardiogram (ECG) with no clinically significant abnormalities
* Subject's pre-study clinical laboratory findings were within normal range or if outside of the normal range were not deemed clinically significant in the opinion of the Investigator
* Subject had bilateral patent nasal airways at screening and Day 1 as assessed by the Investigator
* Subject had a body weight of at least 60 kg

Exclusion Criteria:

* Subject had had a clinically significant illness in the 4 weeks before screening
* Subject used prescribed medications in the 3 weeks prior to dosing or over the counter preparations for 7 days prior to dosing, except paracetamol which was allowed up to 48 hours (h) prior to dosing. Use of multivitamins was permitted
* Subject had a significant history of drug/solvent abuse, or a positive drugs of abuse test at screening
* Subject had a history of alcohol abuse or currently drank in excess of 28 units per week
* Subject currently used tobacco or had a history of smoking within the past 5 years
* Subject was in the opinion of the Investigator not suitable to participate in the study
* Subject had participated in any clinical study with an investigational drug/device within 3 months prior to dosing
* Subject had a positive human immunodeficiency virus (HIV), hepatitis B or hepatitis C screen
* Subject had had a serious adverse reaction or significant hypersensitivity to any drug
* Subject had donated 500 mL or more of blood within the 3 months prior to screening
* Subject had any history of co-existing nasal polyps, NSAID sensitivity and asthma
* Subject had an allergic reaction to aspirin or other NSAIDs
* Subject currently had an upper respiratory tract infection or other respiratory tract condition that could interfere with the absorption of the nasal spray or with the assessment of AEs
* Subject had any suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)
* Subject had used a monoamine oxidase inhibitor in the 14 days prior to study entry
* Subject had an active peptic ulcer disease, gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding
* Subject had anemia due to unexplained or known gastrointestinal bleeding
* Subject had a history of asthma or any other chronic pulmonary disorder
* Subject had renal impairment or a risk of renal failure due to volume depletion
* Subject had a previous history of nasal surgery

Primary outcomes:
measure: Cmax (the maximum observed plasma concentration)
timeFrame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: Tmax (the time to maximum concentration)
timeFrame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: AUC 0-t (the area under the plasma concentration-time curve (AUC) from time zero to the last quantifiable time point post-dose
timeFrame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: AUCinf (the AUC from time zero to infinity, where possible
timeFrame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: t1/2z (the terminal half-life, where possible
timeFrame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose
measure: MRT (the mean residence time)
timeFrame: All PK parameters were assessed using blood samples collected pre-dose, 0.25, 0.5, 0.75, 1, 1.5, 2, 4, 6, 8, 12, and 24 hours post-dose
Secondary outcomes:
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: ICON Development Solutions
Study officials:
affiliation: ICON Development Solutions
name: Cyril Clarke, BSc MB BS MFPM
role: PRINCIPAL_INVESTIGATOR
References: