A Bioequivalence Study of Two Ibuprofen Arginine Granules 400 mg Formulations Under Fasting and Fed Conditions in Chinese Healthy Adult Subjects

NCT05737069 | Completed Phase 1 Results

• 1 other identifier: 218552
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

The primary purpose of this study is to demonstrate the bioequivalence of two ibuprofen arginine granules 400 milligram (mg) formulations under fasting and fed conditions in Chinese healthy adult participants. The secondary purpose of this study is to assess the pharmacokinetic and safety profile of the test and reference preparations.

Conditions

Pain

Outcome Measures

Primary Outcomes (6)

• Area Under the Plasma Concentration Time Curve From Time Zero to Last Observed Concentration at Time t (AUC[0-t]) for Ibuprofen in Fasted Conditions

  AUC(0-t) was defined as area under the plasma concentration-time curve from time zero to last observed concentration at time t calculated using the linear up log down trapezoidal rule. Blood samples were collected at indicated timepoints for the analysis of AUC(0-t). Pharmacokinetic (PK) parameters were determined by non-compartmental analysis.

  Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose

• Area Under the Plasma Concentration Time Curve From Time Zero to Time Infinity (AUC [0-inf]) for Ibuprofen in Fasted Conditions

  AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity, computed as AUC(0-inf) = AUC(0-t) +Ct/λz where Ct was the plasma concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints for the analysis of AUC(0-inf). PK parameters were determined by non-compartmental analysis.

  Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose

• Observed Maximum Plasma Concentration (Cmax) for Ibuprofen in Fasted Conditions

  Cmax was defined as maximum observed post-dose plasma concentration for ibuprofen. Blood samples were collected at indicated timepoints for the analysis of Cmax. PK parameters were determined by non-compartmental analysis.

  Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose

• AUC(0-t) for Ibuprofen in Fed Conditions

  AUC(0-t) was defined as area under the plasma concentration-time curve from time zero to last observed concentration at time t calculated using the linear up log down trapezoidal rule. Blood samples were collected at indicated timepoints for the analysis of AUC(0-t). PK parameters were determined by non-compartmental analysis.

  Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose

• AUC (0-inf) for Ibuprofen in Fed Conditions

  AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity, computed as AUC(0-inf) = AUC(0-t) +Ct/λz where Ct was the plasma concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints for the analysis of AUC(0-inf). PK parameters were determined by non-compartmental analysis.

  Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose

• Cmax for Ibuprofen in Fed Conditions

  Cmax was defined as maximum observed post-dose plasma concentration for ibuprofen. Blood samples were collected at indicated timepoints for the analysis of Cmax. PK parameters were determined by non-compartmental analysis.

  Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose

Secondary Outcomes (8)

• Time to Reach Maximum Plasma Concentration (Tmax) of Ibuprofen in Fasted Conditions

  Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose

• Elimination Half-life (t1/2) of Ibuprofen in Fasted Conditions

  Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose

• Terminal Elimination Rate Constant (λz) of Ibuprofen in Fasted Conditions

  Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose

• Percentage of Extrapolated Area of AUC(0-inf) (%AUCex) of Ibuprofen in Fasted Conditions

  Pre-dose (within 2 hours prior to dosing) and at 5, 10, 15, 20, 30, 45, 60, 75, 90, 105, 120 minutes, 2.5, 3, 4, 6, 8, and 12 hours post-dose

• Tmax of Ibuprofen in Fed Conditions

  Pre-dose (within 2 hours prior to dosing) and 10, 30, 45, 60, 75, 90, 120 minutes, 2.5, 3, 3.5, 4, 4.5, 5, 6, 8, 10 and 12 hours post-dose

Study Arms (2)

Ibuprofen arginine granules 400 mg

EXPERIMENTAL

Participants will be randomly assigned as per cross-over design to receive one sachet of Ibuprofen arginine granules 400 mg (test product) on day 1 of period 1 and will receive one sachet of Ibuprofen arginine granules 400 mg (Spedifen) (reference product) on day 1 of period 2 with at least 2 days washout period. Participants will be instructed to consume the product orally by dissolving it in 240 mL of warm water.

Drug: Ibuprofen arginine granules 400 mg; Drug: Ibuprofen arginine granules 400 mg (Spedifen)

Ibuprofen arginine granules 400 mg (Spedifen)

ACTIVE COMPARATOR

Participants will be randomly assigned as per cross-over design to receive one sachet of Ibuprofen arginine granules 400 mg (Spedifen) (reference product) on day 1 of period 1 and will receive one sachet of Ibuprofen arginine granules 400 mg (test product) on day 1 of period 2 with at least 2 days washout period. Participants will be instructed to consume the product orally by dissolving it in 240 mL of warm water.

Drug: Ibuprofen arginine granules 400 mg; Drug: Ibuprofen arginine granules 400 mg (Spedifen)

Interventions

Ibuprofen arginine granules 400 mg DRUG

Experimental- Ibuprofen arginine granules 400 mg, one sachet administration containing 400 mg ibuprofen granules.

Ibuprofen arginine granules 400 mg; Ibuprofen arginine granules 400 mg (Spedifen)

Ibuprofen arginine granules 400 mg (Spedifen) DRUG

Marketed drug- Ibuprofen arginine granules 400 mg (Spedifen), one sachet administration containing 400 mg ibuprofen granules.

Ibuprofen arginine granules 400 mg; Ibuprofen arginine granules 400 mg (Spedifen)

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Participants provision of a signed and dated informed consent and/or assent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed.
• Participants who is willing and able to comply with scheduled visits, treatment plan, laboratory tests, study restrictions, lifestyle considerations and other study procedures.
• Healthy Participants, which is defined as in general good physical health, as judged by the investigator and no clinically significant relevant abnormalities identified by a detailed medical history, full physical examination, including vital signs, 12-lead electrocardiogram (ECG) and laboratory tests.
• A Participants with a Body Mass Index (BMI) of 19-26 kilogram per meter square (kg/m\^2) (including 19, excluding 26) \[BMI equal to (=) weight (Kilogram \[kg\])/height\^2 (m\^2)\]; and a total body weight more than or equal to \>= 50 kilogram (kg) for males, and \>= 45 kg for females, at screening.
• Participants with one negative polymerase chain reaction (PCR) or antigen test (on Day-1) for active Coronavirus disease 2019 (COVID-19).
• Participants of childbearing potential and are sexually active and at risk for pregnancy must agree to use a highly effective method of contraception throughout the study and for at least 30 days after the last dose of assigned treatment. Female participant who are not of childbearing potential must meet requirements in the Contraception section of protocol.

You may not qualify if:

• Known or suspected intolerance or hypersensitivity or photosensitivity to the investigational products (or closely related compounds) or any of their stated ingredients.
• Allergy to skin disinfecting agents, tape, or latex rubber, whenever appropriate substitutions cannot be applied or in the investigator's opinion may pose a risk to the candidate.
• Diagnosis of long QT syndrome or QTcF \> 450 millisecond (msec) at screening.
• Clinically significant vital sign abnormalities (systolic blood pressure lower than 90 or over 140 millimeters of mercury (mmHg), diastolic blood pressure lower than 60 or over 90 mmHg, or pulse rate less than 50 or over 100 beats per minute \[bpm\]).
• Use of any medication (including over-the-counter medications and Chinese herbal and traditional remedies) within 2 weeks before first scheduled study drug administration or within less than 10 times the elimination half-life of the concomitant medication (whichever is longer) or is anticipated to require any concomitant medication during that period or at any time throughout the study. Allowed treatments are:
• systemic contraceptives and hormone replacement therapy, as long as female participant is on stable treatment for at least 3 months before first scheduled study drug administration and continues treatment throughout the study.
• occasional use of acetaminophen (up to 2 grams \[g\] in 24 hours).
• Participants has a history of drug abuse or has positive urine drug abuse screening at screening or on Day-1.
• Participants reported regular consumption of \> 5 cups (1 cup approximately 250 milliliters \[mL\]) of coffee or tea per day (or equivalent consumption of \>= 500 mg caffeine per day using other products). Or consuming any beverages or food containing caffeine, such as coffee, tea, coke, chocolate, etc., within 48 hours prior to screening.
• Smoking or history of regular use of tobacco- or nicotine-containing products (for example nicotine patch, electronic cigarette) within 6 months prior to screening. Or a participant who is unwilling to abstain from tobacco or nicotine containing product use during the study.
• Evidence, as reported by an alcohol breath testing, for current alcohol abuse or reports a regular average alcohol consumption exceeding 18 g (women) or 35 g (men) of pure alcohol per day, that is (i.e.) 1 drink/day for women or 2 drinks/day for men \[1 drink = 5 ounces (150 mL) of wine or 12 ounces (360 mL) of beer or 1.5 ounces (45 mL) of hard liquor\] within 6 months prior to screening.
• Participation in other clinical trials involving investigational drug(s) within 90 days prior to screening.
• Those who have blood donation (including component donation) or blood loss \>= 400 mL within 3 months before the study or have blood transfusion; those who have blood donation (including component donation) or blood loss \>= 200 mL within 1 month before the study (except female physiological blood loss).
• Acute or chronic medical condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the participant inappropriate for entry into this study. Or any condition not identified in the protocol that in the opinion of the investigator would confound the evaluation and interpretation of the study data or may put the participant at risk.
• Evidence or history of clinically significant hematological, renal, endocrine, pulmonary, cardiovascular, hepatic, psychiatric, neurologic, or allergic disease within the last 5 years that may increase the risk associated with study participation.

Sponsors & Collaborators

• HALEON: lead

Study Sites (1)

Clinical Pharmacological Research Center

Wenjiang, Chengdu, 611130, China

Location

MeSH Terms

Conditions

Pain

Interventions

ibuprofen arginine

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Results Point of Contact

• Title: Haleon Response Center
• Organization: HALEON

ww.clinical-trial-register@haleon.com

+441932959500

Study Officials

• Min Xu, Master

  Clinical Pharmacological Research Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

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

Study Record Dates

• First Submitted: February 10, 2023
• First Posted: February 21, 2023
• Study Start: April 19, 2023
• Primary Completion: May 15, 2023
• Study Completion: May 15, 2023
• Last Updated: September 19, 2024
• Results First Posted: September 19, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: IPD will be made available within 6 months of publishing the results of the primary endpoints, key secondary endpoints and safety data of the study.
• Access Criteria: Access is provided after a research proposal is submitted and has received approval from the Independent Review Panel and after a Data Sharing Agreement is in place. Access is provided for an initial period of 12 months, but an extension can be granted, when justified, for up to another 12 months.

Locations

CN (1)