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Study to Determine the Tolerability, Safety and Pharmacokinetics of Ketorolac Tromethamine by Intranasal Administration in Healthy Volunteers

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ClinicalTrials.gov Identifier: NCT01363050
Recruitment Status : Completed
First Posted : June 1, 2011
Results First Posted : May 3, 2013
Last Update Posted : March 16, 2017
Sponsor:
Information provided by (Responsible Party):
Egalet Ltd

Tracking Information
First Submitted Date  ICMJE May 27, 2011
First Posted Date  ICMJE June 1, 2011
Results First Submitted Date  ICMJE August 29, 2012
Results First Posted Date  ICMJE May 3, 2013
Last Update Posted Date March 16, 2017
Study Start Date  ICMJE January 2006
Actual Primary Completion Date February 2006   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 19, 2013)
  • Cmax (the Maximum Observed Plasma Concentration) [ Time Frame: 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) ]
    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.
  • Tmax (the Time to Maximum Concentration) [ Time Frame: 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) ]
    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.
  • AUC 0-8h (the Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose) [ Time Frame: 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) ]
    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.
  • Cmax,ss (the Maximum Observed Plasma Concentration at Steady State) [ Time Frame: 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 3 (morning doses) ]
    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.
  • Tmax,ss (the Time to Maximum Concentration at Steady State) [ Time Frame: 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 3 (morning doses) ]
    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.
  • Cmin,ss (the Minimum Observed Plasma Concentration at Steady State) [ Time Frame: 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 3 (morning doses) ]
    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.
  • Tmin,ss (the Time to Minimum Concentration at Steady State) [ Time Frame: 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 3 (morning doses) ]
    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.
  • AUCτ (the Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady-state) [ Time Frame: 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 3 (morning doses) ]
    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.
  • MRT (the Mean Residence Time [ Time Frame: 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 3 (morning doses) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: May 27, 2011)
  • Cmax (the Maximum Observed Plasma Concentration) [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
  • Tmax (the Time to Maximum Concentration) [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
  • AUC 0-8h (the Area Under the Plasma Concentration-time Curve From Time 0 to 8 Hours Post-dose) [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
  • Cmax,ss (the Maximum Observed Plasma Concentration at Steady State) [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
  • Tmax,ss (the Time to Maximum Concentration at Steady State) [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
  • Cmin,ss (the Minimum Observed Plasma Concentration at Steady State) [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
  • Tmin,ss (the Time to Minimum Concentration at Steady State) [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
  • AUCτ (the Area Under the Plasma Concentration-time Curve Over the Dosing Interval at Steady-state) [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
  • MRT (the Mean Residence Time [ Time Frame: For all PK analyses 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 Days 1 and 3 (morning doses) ]
    PK analysis by standard model independent methods was perfromed 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, togather with the individual plasma concentrations of ketorolac.
Change History Complete list of historical versions of study NCT01363050 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Study to Determine the Tolerability, Safety and Pharmacokinetics of Ketorolac Tromethamine by Intranasal Administration in Healthy Volunteers
Official Title  ICMJE A Phase 1, Open Label, Multiple Dose Study to Determine the Tolerability, Safety and Pharmacokinetics of Ketorolac Tromethamine by Intranasal Administration in Healthy Volunteers
Brief Summary

This was a phase 1, open label, multiple dose study in healthy male and female volunteers. 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.

The objective of this study in healthy volunteers was to determine the safety, tolerability, and pharmacokinetics of multiple doses of intranasal ketorolac tromethamine.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Healthy Volunteers
Intervention  ICMJE Drug: 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.
Study Arms  ICMJE Experimental: Ketorolac tromethamine
Intervention: Drug: Ketorolac tromethamine
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: May 27, 2011)
15
Original Actual Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2006
Actual Primary Completion Date February 2006   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 60 Years   (Adult)
Accepts Healthy Volunteers  ICMJE Yes
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01363050
Other Study ID Numbers  ICMJE ROX 2005-03
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Egalet Ltd
Study Sponsor  ICMJE Egalet Ltd
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Cyril Clarke, BSc MB BS MFPM Medeval Limited
PRS Account Egalet Ltd
Verification Date February 2017

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP