Study to Determine the Tolerability, Safety and Pharmacok... | NCT01363050

NCT01363050

Protocol Section

Identification Module

Results Section

Participant Flow Module

Annotation Section

No data available

No data is available for this block.

Document Section

No data available

No data is available for this block.

Derived Section

Miscellaneous Info Module

Status Module

Label	Type	Description	Intervention Names
Ketorolac tromethamine	Experimental		Drug: Ketorolac tromethamine

Name	Type	Description	Arm Group Labels	Other Names
Ketorolac tromethamine	Drug	Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
Cmax (the Maximum Observed Plasma Concentration)	PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.	Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 1 (morning doses)
Tmax (the Time to Maximum Concentration)	PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.	Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 1 (morning doses)
AUC 0-8h (the Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose)	PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.	Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 1 (morning doses)
Cmax,ss (the Maximum Observed Plasma Concentration at Steady State)	PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Eligibility Module

Eligibility Criteria

Inclusion Criteria:

Male or female volunteers, aged 18 to 60 years inclusive
Female subjects of child bearing potential were to have a negative urine pregnancy test prior to entry into the study and must not have been breast feeding
All female subjects of child bearing potential and all male subjects with female partners of child bearing potential must have consented to using a medically acceptable method of contraception (oral or implanted contraceptive hormones, condom or diaphragm with spermicidal agent, intrauterine device or surgical sterilisation) throughout the study period
Subject had given signed informed consent
Subject was within 20% of normal weight for his/her 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 ECG with no clinically significant abnormalities
Subject's pre-study clinical laboratory findings were within normal range or, if outside of the normal range, not deemed clinically significant in the opinion of the Investigator
Subject had bilateral patent nasal airways at screening as assessed by the Investigator
Body weight of at least 60 kg

Exclusion Criteria:

Subject had a clinically significant illness in the four weeks prior to screening
Use of prescribed medications in the three weeks prior to dosing or over-the-counter preparations for seven days prior to dosing, except paracetamol which was allowed up to 48 hours prior to dosing. Use of multivitamins and oral contraceptives were permitted
Subject had a significant history of drug/solvent abuse, or a positive drugs of abuse test at screening
Subjects with a history of alcohol abuse or those currently drinking more than 28 units per week (males) or 21 units per week (females)
Current tobacco use or a history of smoking within the past five years
Subject was, in the opinion of the Investigator, not suitable to participate in the study
Subjects who had participated in any clinical study with an investigational drug/device within three months prior to the first day of dosing
Subjects who had a positive result of HIV screen, Hepatitis B screen or Hepatitis C screen
Subjects who had a serious adverse reaction or significant hypersensitivity to any drug
Subjects having donated 500 mL or more of blood within the three months prior to screening
Any history of co-existing nasal polyps, NSAID sensitivity and asthma
Allergic reaction to aspirin or other NSAIDs
Current upper respiratory tract infection or other respiratory tract condition that may have interfered with the absorption of the nasal spray or with the assessment of adverse events (AEs)
Any suspicion of rhinitis medicamentosa (chronic daily use of topical decongestants)
Use of a monoamine oxidase inhibitor (MAOI) in the 14 days prior to study entry
Active peptic ulcer disease, gastrointestinal bleeding or perforation, or a history of peptic ulcer disease or gastrointestinal bleeding
Anemia due to unexplained or known gastrointestinal bleeding
History of asthma or any other chronic pulmonary disorder
Renal impairment or a risk of renal failure due to volume depletion
Known sensitivity to lidocaine hydrochloride

Name	Affiliation	Role
Cyril Clarke, BSc MB BS MFPM	Medeval Limited	Principal Investigator

ID	Title	Description
FG000	Ketorolac Tromethamine	Ketorolac tromethamine : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.

ID	Title	Description
BG000	Ketorolac Tromethamine	Ketorolac tromethamine : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.

Units	Counts
Participants	BG000

Title	Description	Population Description	Parameter Type	Dispersion Type	Unit of Measure	Calculate Percentage	Denominator Units Selected	Denominators	Classes
Age, Categorical			Count of Participants

Outcome Measures Module

Outcome Measures

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

Cmax (the Maximum Observed Plasma Concentration)

PK analysis by standard model independent methods was performed by a pharmacokineticist using WinNonlin Professional. Actual blood sampling times were converted to a time from dosing (elapsed time). Elapsed times were listed by subject for each treatment, together with the individual plasma concentrations of ketorolac.

Two subjects were considered pharmacokinetic outliers and were excluded from the PK population.

Posted

Mean

Standard Deviation

ng/mL

Blood samples for determination of plasma concentration of ketorolac were taken immediately prior to each dose and every hour for 8 hours post-dose on Day 1 (morning doses)

ID	Title	Description
OG000	Ketorolac Tromethamine	Ketorolac tromethamine (Day 1) : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.

Adverse Events Module

Arm/Groups

ID	Title	Description	Deaths (Affected)	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Ketorolac Tromethamine	Ketorolac tromethamine : Subjects received intranasal ketorolac tromethamine (30 mg) three times daily (t.i.d.) for three days (seven doses in total). Doses were administered every eight hours.

ID	Term
D007213	Indomethacin
D007211	Indoles
D006574	Heterocyclic Compounds, 2-Ring
D000072471	Heterocyclic Compounds, Fused-Ring