Crossover, Single Dose Randomized, Bioequivalence of Ketoprofen Lysine Salt Immediate Release vs Oral Solution

NCT02350296 | Completed Phase 1 Results

• 1 other identifier: KSL0114
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Objectives: The objective of the study was to investigate the bioequivalence between two formulations containing ketoprofen lysine salt (KLS) when administered as single oral doses in two consecutive study periods to healthy male and female volunteers under fasting conditions. Primary end-point: to evaluate the bioequivalent rate (Cmax) and extent (AUC0-t) of absorption of ketoprofen after single dose administration of test and reference products. Secondary end-points:

• to describe the pharmacokinetic (PK) profile of ketoprofen after single dose administration of test and reference products;
• to collect safety and tolerability data after single dose administration of test and reference products.

Conditions

Pain Disorders

Keywords

headache; dental pain; neuralgia; dysmenorrhoea; muscular and osteoarticular pain

Outcome Measures

Primary Outcomes (2)

• Ketoprofen Plasma PK Parameters: Cmax

  Cmax = maximum plasma concentration. Cmax a of ketoprofen was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentrations of ketoprofen were measured in each study period at the timepoints hereunder reported. Arithmetic means + standard deviation are reported hereunder.

  0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dose

• Ketoprofen Plasma PK Parameters: AUC0-t

  AUC0-t = Area under the concentration-time curve from administration to the last observed concentration time t, calculated with the linear trapezoidal method. AUC0-t of ketoprofen was calculated from plasma concentrations after single oral dose of test and reference products. Plasma concentrations of ketoprofen were measured in each study period at the timepoints hereunder specified. Please note that AUC0-t was considered a reliable estimate of the extent of absorption if the ratio AUC0-t/AUC0-∞ equalled or exceeded a factor of 0.8, i.e. if %AUCextra was \< 20%. Arithmetic means + standard deviation are reported hereunder.

  pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose.

Secondary Outcomes (5)

• Ketoprofen Plasma PK Parameters: AUC0-∞

  pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose

• Ketoprofen Plasma PK Parameters: Tmax

  pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose.

• Ketoprofen Plasma PK Parameters: T1/2

  pre-dose (0), 5, 15, 30, 45 min, 1, 1.5, 2, 3, 4, 5, 6 and 8 h post-dose.

• Ketoprofen Plasma PK Parameters: Frel

  0, 1, 2, 3, 4, 5, 6, 7 and 8 hours post-dose

• Number of TEAEs

  From Day -14 to Day 1 of period 2 (Final visit/ETV), approximately 1 month

Study Arms (2)

Test - Reference (KSL 40 mg - OKi® 80 mg)

EXPERIMENTAL

In this arm, a single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in the first study period (day 1, 08:00±1h), and, after a wash-out period of at least 4 days, a single dose of the reference product OKi® 80 mg (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in the second study period (day 1, Visit 5, 08:00 ±1h).

Drug: KSL 40 mg; Drug: OKi® 80 mg

Reference - Test (OKi® 80 mg - KSL 40 mg)

EXPERIMENTAL

In this arm, a single dose of the reference product OKi® 80 mg (half a sachet, 40 mg KLS) was orally administered, under fasting conditions, in the first study period (day 1, Visit 3, 08:00 ±1h) and, after a wash-out period of at least 4 days, a single dose of the test product (1 tablet; 40 mg KLS) was orally administered, under fasting conditions, in the second study period (day 1, Visit 5, 08:00±1h).

Drug: KSL 40 mg; Drug: OKi® 80 mg

Interventions

KSL 40 mg DRUG

Ketoprofen lysine salt (KLS) immediate release oral tablets 40 mg, corresponding to 25 mg of ketoprofen free acid. Ketoprofen lysine salt was administered according to the randomisation list and the cross-over design. One (1) tablet of test formulation was administered to the subjects in the morning with 240 mL of still mineral water. Afterwards, no fluid intake was permitted for 2 h. All subjects were under fasting conditions from the evening before investigational product administration (i.e. for at least 10 h, overnight).

Also known as: Ketoprofen lysine salt

Reference - Test (OKi® 80 mg - KSL 40 mg); Test - Reference (KSL 40 mg - OKi® 80 mg)

OKi® 80 mg DRUG

OKi® 80 mg granules for oral solution (bipartite sachets: each half sachet containing 40 mg of KLS corresponding to 25 mg of ketoprofen free acid). Ketoprofen lysine salt was administered according to the randomisation list and the cross-over design. The content of half sachet of the reference formulation was dissolved in 190 mL of still mineral water. The subject drank the entire solution immediately. Then the glass was rinsed with 50 mL of still mineral water and the subject drank the rinse immediately. Afterwards, no fluid intake was permitted for 2 h. All subjects were under fasting conditions from the evening before investigational product administration (i.e. for at least 10 h, overnight).

Also known as: Ketoprofen lysine salt

Reference - Test (OKi® 80 mg - KSL 40 mg); Test - Reference (KSL 40 mg - OKi® 80 mg)

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• To be enrolled in this study, subjects must fulfil all these criteria:
• Sex and Age: males/females, 18-55 years old inclusive
• Body Mass Index (BMI): 18.5-30 kg/m2 inclusive
• Vital signs: systolic blood pressure (SBP) 100-139 mmHg, diastolic blood pressure (DBP) 50-89 mmHg, pulse rate (PR) 50-90 bpm and body temperature (BT) ≤ 37.5° C, measured after 5 min of rest in the sitting position;
• Full comprehension: ability to comprehend the full nature and purpose of the study, including possible risks and side effects; ability to co-operate with the investigator and to comply with the requirements of the entire study
• Contraception and fertility (females only): females of child-bearing potential and with an active sexual life must be using at least one of the following reliable methods of contraception:
• Hormonal oral, implantable, transdermal, or injectable contraceptives for at least 2 months before the screening visit
• A non-hormonal intrauterine device \[IUD\] or female condom with spermicide or contraceptive sponge with spermicide or diaphragm with spermicide or cervical cap with spermicide for at least 2 months before the screening visit
• A male sexual partner who agrees to use a male condom with spermicide
• A sterile sexual partner
• Female participants of non-child-bearing potential or in post-menopausal status for at least 1 year will be admitted. For all female subjects, pregnancy test result must be negative at screening.

You may not qualify if:

• Subjects meeting any of these criteria will not be enrolled in the study:
• Electrocardiogram (ECG 12-leads, supine position): clinically significant abnormalities
• Physical findings: clinically significant abnormal physical findings which could interfere with the objectives of the study
• Laboratory analyses: clinically significant abnormal laboratory values indicative of physical illness
• Allergy: ascertained or presumptive hypersensitivity to the active principles (ketoprofen) and/or formulations' ingredients; history of hypersensitivity to drugs (in particular to NSAIDs) or allergic reactions in general, which the Investigator considers may affect the outcome of the study
• Diseases: significant history of renal, hepatic, gastrointestinal, cardiovascular, respiratory (including asthma), skin, haematological, endocrine or neurological and autoimmune diseases that may interfere with the aim of the study
• Medications: medications, including over the counter (OTC) drugs \[in particular ketoprofen and acetylsalicylic acid (ASA) and NSAIDs in general\], herbal remedies and food supplements taken 2 weeks before the start of the study. Hormonal contraceptives for females will be allowed
• Investigative drug studies: participation in the evaluation of any investigational product for 3 months before this study. The 3-month interval is calculated as the time between the first calendar day of the month that follows the last visit of the previous study and the first day of the present study (date of the informed consent signature)
• Blood donation: blood donations for 3 months before this study
• Drug, alcohol, caffeine, tobacco: history of drug, alcohol \[\> 1 drink/day for females and \> 2 drinks/day for males, defined according to the USDA Dietary Guidelines 2010 (6)\], caffeine (\> 5 cups coffee/tea/day) or tobacco abuse (≥ 6 cigarettes/day)
• Drug test: positive result at the drug test at screening
• Alcohol test: positive alcohol breath test at day -1
• Diet: abnormal diets (\< 1600 or \> 3500 kcal/day) or substantial changes in eating habits in the 4 weeks before this study; vegetarians
• Pregnancy (females only): positive or missing pregnancy test at screening or day -1, pregnant or lactating women

Sponsors & Collaborators

• Dompé Farmaceutici S.p.A: lead
• Cross Research S.A.: collaborator

Study Sites (1)

CROSS Research S.A., Phase I Unit

Arzo, CH-6864, Switzerland

Location

MeSH Terms

Conditions

Somatoform Disorders; Headache; Toothache; Neuralgia; Dysmenorrhea

Condition Hierarchy (Ancestors)

Mental Disorders; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Tooth Diseases; Stomatognathic Diseases; Facial Pain; Peripheral Nervous System Diseases; Neuromuscular Diseases; Nervous System Diseases; Menstruation Disturbances; Pathologic Processes; Pelvic Pain

Results Point of Contact

• Title: Clinical Development & Operations
• Organization: Dompé farmaceutici SpA

clinical.trials@dompe.com

+39 02 583831

Study Officials

• Milko Radicioni, MD

  CROSS Research S.A., Phase I Unit

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 15, 2014
• First Posted: January 29, 2015
• Study Start: November 26, 2014
• Primary Completion: December 16, 2014
• Study Completion: April 22, 2015
• Last Updated: April 19, 2024
• Results First Posted: April 19, 2024

Record last verified: 2024-04

Locations

CH (1)