PainPhase 1NCT05674721

A Bioequivalence Study of Advil PM Liqui-Gels Minis (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) Compared to the Current Marketed Advil PM Liqui-Gels (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) in Healthy Adult Subjects Under Fasted Conditions

A Phase 1 study testing Advil PM Liqui-Gels Minis and Advil PM Liqui-Gels in people with Pain, run by HALEON at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

The purpose of this study is to support the submission of Advil PM Liqui-Gels Minis (ibuprofen/diphenhydramine hydrochloride 200 milligrams [mg]/25 mg) which is a size reduction of the currently marketed Advil PM Liqui-Gels, by determining if this product is bioequivalent to the reference product Advil PM Liqui-Gels… Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: Pain
What is being tested?: Advil PM Liqui-Gels Minis and Advil PM Liqui-Gels
Type of treatment: Pill or oral medicine
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 77 participants
Where: 1 siteUnited States
Study dates: 5 Jan 2023to 21 Mar 2023
Phase: Phase 1
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed.
Participant who is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Healthy participant, which is defined as in general good physical health, as judged by the investigator and no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead Electrocardiogram (ECG) or clinical laboratory tests.
Body Mass Index (BMI) of 18.5 to 30.0 Kilogram per meter square (kg/m^2); and a total body weight greater than or equal to (>=)50.0 Kilogram (kg) for males and >=45.0 kg for females.
Female participant of childbearing potential 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 is not of childbearing potential must meet at least one of the following criteria: A. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level >= 40 mili international unit per milliliter (mIU/mL) B. Have undergone a documented (including self-reported) hysterectomy and/or bilateral oophorectomy.
Participant with two negative tests (one at screening within 72 hours of admission and one at check in Day-1 in Period 1) for active coronavirus disease 2019 (COVID-19), separated by more than (>)24 hours.

Who cannot join

Participant who is an investigational site staff member directly involved in the conduct of the study and his/her family members, site staff member otherwise supervised by the Investigator, or participant who is a GlaxoSmithKline (GSK) employee directly involved in the conduct of the study.
Participation in other studies involving investigational drug(s) within 30 days prior to study entry and/or during study participation.
Acute or chronic medical or psychiatric 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.
Pregnant female participant as confirmed by a positive pregnancy test or intending to become pregnant over the duration of the study.
Breastfeeding female participant.
Known or suspected intolerance or hypersensitivity to the study materials (or closely related compounds) or any of their stated ingredients (gelatin, medium-chain triglycerides, pharmaceutical ink, polyethylene glycol, potassium hydroxide, purified water, sorbitol sorbitan solution).

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Any history of asthma, urticaria, or other significant allergic diathesis or allergic reaction to any other pain reliever/fever reducer. Participant with uncomplicated seasonal allergic rhinitis can be accepted if expected allergy season is clearly outside enrollment/treatment period.
Diagnosis of long QT syndrome or QTcF > 450 millisecond (msec) for males and > 470 msec for females 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 50 or over 90 mmHg, or pulse rate less than 50 or over 100 beats per minute [bpm]).
Unwilling or unable to comply with the Lifestyle Considerations described in this protocol.
Use of any medication (including over the counter [OTC] medications and herbal remedies) within 2 weeks or within less than 10 times the elimination half-life of the respective drug (whichever is longer) before first scheduled study drug administration 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] daily).
Evidence or history of clinically significant laboratory abnormality, 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.
Clinically relevant chronic or acute infectious illnesses or febrile infections within two weeks prior to start of the study.
Any surgical or medical condition which may significantly alter the absorption, distribution, metabolism or excretion of any drug substance but not limited to any of the following:
History of major gastrointestinal tract surgery such as gastrectomy, gastroenterostomy, bowel resection, gastric bypass, gastric stapling or gastric banding (note: this is not applicable for minor abdominal surgery without significant tissue resection, for example, appendectomy and herniorrhaphy).
History of inflammatory bowel disease or gastrointestinal bleeding including peptic ulcers.
History or current evidence of renal disease or impaired renal function at screening as indicated by abnormal levels of serum creatinine (> 1.43 milligram/deciliter [mg/dL]) or blood urea nitrogen (BUN) (>= 35 mg/dL) or the presence of clinically significant abnormal urinary constituents (e.g., albuminuria).
History or current evidence of ongoing hepatic disease or impaired hepatic function at screening. A participant will be excluded if more than one of the following lab value deviations are found: 1) Aspartate aminotransferase (AST) (>= 1.2 upper limit of normal [ULN]), Alanine transaminase (ALT) (>= 1.2 ULN), 2) Gamma-glutamyl transferase (GGT) (>= 1.2 ULN), Alkaline phosphatase (ALP) (>= 1.2 ULN), 3) total bilirubin (> 2.00 mg/dL) or creatine kinase (>= 3 ULN). A single deviation from the above values is acceptable and will not exclude the candidate, unless specifically advised by the investigator.
Evidence of urinary obstruction (for example, due to benign prostate hyperplasia) or difficulty in voiding at screening.
Diagnosis of angle-closure (narrow angle) glaucoma.
History or clinical evidence at screening of pancreatic injury or pancreatitis.
Participant with signs and symptoms suggestive of COVID-19 (for example, fever, cough, and so on within 14 days of inpatient admission as defined by World Health Organization (WHO) or local guidance.
Participant with known COVID-19 positive contacts in the past 14 days.
Any vaccination, including COVID-19 vaccine, within 14 days prior to the first dose.
History of drug abuse within 1 year prior to screening or recreational use of soft drugs (such as marijuana) within 1 month or hard drugs (such as cocaine, phencyclidine [PCP], crack, opioid derivatives including heroin, and amphetamine derivatives) within 3 months prior to screening.
History of alcohol abuse within 1 year prior to screening or regular use of alcohol within 6 months prior to screening that exceeds 10 units for women or 15 units for men of alcohol per week (1 unit = 340 mL of beer 5 percent [%], 140 mL of wine 12%, or 45 mL of distilled alcohol 40%).
Positive urine drug screen or alcohol breath test at screening.
Participant reported regular consumption of beverages or food containing xanthine derivatives or xanthine-related compounds (for example, coffee, tea, caffeine-containing sodas and chocolate), equivalent to >= 500 mg xanthine per day.
Current smoker, defined as the use of tobacco or nicotine products during the 3 months prior to screening until admission to the unit or a positive urine cotinine test at screening.
Participant reports consumption of any drug metabolizing enzyme (e.g., CYP3A4 or other cytochrome P450 enzymes) inducing or inhibiting aliments, beverages or food supplements (for example, broccoli, Brussels sprouts, grapefruit, grapefruit juice, star fruit, St. John's Wort and so on) within 2 weeks prior to admission to the unit.
Performance of strenuous physical exercise (body building, high performance sports) from 2 weeks prior to admission and throughout the entire study.
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 Participant.
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.
Donation of plasma within 7 days prior to dosing or donation or loss of 500 mL or more of whole blood within 8 weeks prior to dosing.
Hemoglobin value less than (<)12.0 grams per deciliter (g/dL) for males and < 11.5 g/dL for females.
Participant who has previously been enrolled in this study.

Trial locations and contacts

1 site in 1 country.

United States1 site

Syneos Health
Miami, Florida, 33144

Other trials in United States

About this study

Official title: A Randomized, Open Label, Single Center, Single Dose, Two Treatment, Two Period, Two Sequence Crossover Bioequivalence Study of Advil PM Liqui-Gels Minis (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) To Advil PM Liqui-Gels (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) in Healthy Adult Subjects Under Fasted Conditions

Read the detailed description

This is a single center, single dose, open-label, randomized, two-treatment, two-sequence, two-period crossover, bioequivalence study in healthy adult participants with at least a 7-day washout period. A sufficient number of participants will be screened to randomize approximately 44 to ensure at least 37 evaluable participants complete the entire study. Participants will be randomly assigned to one of 2 treatment sequences and receive a single dose of one of the treatments in each period following a crossover design.

Conditions: Pain
Being tested: Advil PM Liqui-Gels Minis, Advil PM Liqui-Gels
Medical subject headings: Pain

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Advil PM Liqui-Gels MinisDrug
Ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg, Oral capsule which is a size reduction of the currently marketed reference product.
Advil PM Liqui-GelsDrug
Ibuprofen/diphenhydramine hydrochloride 200 mg/25 mg, Oral capsule.

Study groups in NCT05674721
Study group	Role	What they receive
Advil PM Liqui-Gels Minis	Experimental	Participants will be randomly assigned as per cross-over design to receive a single dose of 2 Advil PM Liqui-Gels Minis capsules orally on day 1 of period 1 and will receive single dose of 2 Advil PM Liqui-Gels capsules orally on day 1 of period 2 with at least 7 days washout period. Participants will be instructed to consume the entire amount of ambient temperature water (approximately 240 milliliters [mL]) along their investigational product. Receives: Drug: Advil PM Liqui-Gels Minis
Advil PM Liqui-Gels	Active comparator	Participants will be randomly assigned as per cross-over design to receive a single dose of 2 Advil PM Liqui-Gels capsules orally on day 1 of period 1 and will receive single dose of 2 Advil PM Liqui-Gels Minis capsules orally on day 1 of period 2 with at least 7 days washout period. Participants will be instructed to consume the entire amount of ambient temperature water (approximately 240 mL) along their investigational product. Receives: Drug: Advil PM Liqui-Gels

What is being measured

The primary outcome is the main question the study is designed to answer.

Maximum Observed Plasma Concentration (Cmax) for Ibuprofen
Cmax was defined as maximum observed post-dose plasma concentration for ibuprofen obtained without interpolation. Blood samples were collected at indicated timepoints and pharmacokinetic (PK) analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Cmax for Diphenhydramine
Cmax was defined as maximum observed post-dose plasma concentration for diphenhydramine obtained without interpolation. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to the Last Measurable Sampling Time Point (t) (AUC [0-t]) for Ibuprofen
AUC (0-t) was defined as the area under the plasma concentration versus time curve calculated from time zero to the last measurable sampling time point, (t) using linear up log down trapezoidal method. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
AUC (0-t) for Diphenhydramine
AUC (0-t) was defined as the area under the plasma concentration versus time curve calculated from time zero to the last measurable sampling time point, (t) using linear up log down trapezoidal method. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to Infinity (AUC [0-inf]) for Ibuprofen
AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity, computed as AUC0-inf = AUC0-t + C(last)/λz where C(last) was the concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
AUC (0-inf) for Diphenhydramine
AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity computed as AUC0-inf = AUC0-t + C(last)/λz where C(last) was the concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)

Secondary outcomes (11)

Terminal Elimination Rate Constant (λz) for Ibuprofen
λz was computed as negative of the estimated slope of the linear regression of the ln-transformed concentration versus time profile in the terminal elimination phase. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
λz for Diphenhydramine
λz was computed as the negative of the estimated slope of the linear regression of the ln-transformed concentration versus time profile in the terminal elimination phase. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Time of the Maximum Observed Post-dose Concentration (Tmax) for Ibuprofen
tmax was defined as time of the maximum observed post-dose concentration. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Tmax for Diphenhydramine
tmax was defined as time of the maximum observed post-dose concentration. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
The Elimination Half-life (t1/2) for Ibuprofen
Elimination half-life was computed as t1/2 = ln(2)/λz where λz is the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
t1/2 for Diphenhydramine
Elimination half-life was computed as t1/2 = ln(2)/λz where λz is the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Apparent Volume of Distribution (Vz/F) for Ibuprofen
Vz/F was calculated by the dose administered/(λz*AUC0-inf) where λz was the terminal elimination rate constant and AUC0-inf was area under the plasma concentration versus time curve calculated from time 0 to infinity. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Vz/F for Diphenhydramine
Vz/F was calculated by the dose administered/(λz*AUC0-inf) where λz is the terminal elimination rate constant and AUC0-inf is area under the plasma concentration versus time curve calculated from time 0 to infinity. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Apparent Total Clearance (CI/F) for Ibuprofen
CI/F was calculated as dose administered/AUC0-inf where AUC0-inf was area under the plasma concentration versus time curve calculated from time zero to infinity. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
CI/F for Diphenhydramine
CI/F was calculated as dose administered/ AUC0-inf where AUC0-inf was area under the plasma concentration versus time curve calculated from time zero to infinity. Blood samples were collected at indicated timepoints and PK analysis was performed.
Measured: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Number of Participants Reporting Ease of Swallowing on 5-Point Ordinal Scale
Immediately after dosing, the assessment of 'ease of swallowing' was done via one question with an ordinal response (ease of swallowing on 5-point ordinal scale) of each product. Participants ranked the 'ease of swallowing' of the product on a scale from 1 to 5 where 1=not easy to swallow; 2=somewhat easy to swallow; 3=average to swallow; 4=above average to swallow; 5=very easy to swallow. Higher score indicated more ease in swallowing.
Measured: Post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

5 Jan 202321 Mar 2023

First posted6 Jan 2023
Study start5 Jan 2023
Primary completion21 Mar 2023
Study completion21 Mar 2023

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Other trials for PainStudies of the same condition, open and under way.
More trials run by HALEONThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Enrolment: 77 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05674721
Sponsor's protocol ID: 218677
Status last verified: Aug 2024
First submitted: 16 Dec 2022
Last updated: 23 Aug 2024
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: Yes: Anonymized individual participant data and study documents can be requested for further research from ww.clinical-trial-register@haleon.com

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

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Study at a glance

From the registry record, last updated by the sponsor on 23 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Randomized, Open Label, Single Center, Single Dose, Two Treatment, Two Period, Two Sequence Crossover Bioequivalence Study of Advil PM Liqui-Gels Minis (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) To Advil PM Liqui-Gels (Ibuprofen/Diphenhydramine Hydrochloride 200 mg/25 mg) in Healthy Adult Subjects Under Fasted Conditions
ClinicalTrials.gov ID: NCT05674721
Acronym / sponsor ID: 218677
Conditions: Pain
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 77 participants (actual)
Lead sponsor: HALEONIndustry (pharma, biotech, devices)
Study start: 5 Jan 2023 (actual)
Primary completion: 21 Mar 2023 (actual)
Study completion: 21 Mar 2023 (actual)
First posted: 6 Jan 2023 (actual)
Results: Posted 23 Aug 2024

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: None (open label)
Number of arms: 2

Arm	Type	Receives
Advil PM Liqui-Gels Minis	Experimental	Drug: Advil PM Liqui-Gels MinisParticipants will be randomly assigned as per cross-over design to receive a single dose of 2 Advil PM Liqui-Gels Minis capsules orally on day 1 of period 1 and will receive single dose of 2 Advil PM Liqui-Gels capsules orally on day 1 of period 2 with at least 7 days washout period. Participants will be instructed to consume the entire amount of ambient temperature water (approximately 240 milliliters [mL]) along their investigational product.
Advil PM Liqui-Gels	Active comparator	Drug: Advil PM Liqui-GelsParticipants will be randomly assigned as per cross-over design to receive a single dose of 2 Advil PM Liqui-Gels capsules orally on day 1 of period 1 and will receive single dose of 2 Advil PM Liqui-Gels Minis capsules orally on day 1 of period 2 with at least 7 days washout period. Participants will be instructed to consume the entire amount of ambient temperature water (approximately 240 mL) along their investigational product.

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (6 listed)

Evidence of a personally signed and dated informed consent document indicating that the participant has been informed of all pertinent aspects of the study before any assessment is performed.
Participant who is willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
Healthy participant, which is defined as in general good physical health, as judged by the investigator and no clinically relevant abnormalities identified by a detailed medical history, full physical examination, including blood pressure and pulse rate measurement, 12-lead Electrocardiogram (ECG) or clinical laboratory tests.
Body Mass Index (BMI) of 18.5 to 30.0 Kilogram per meter square (kg/m^2); and a total body weight greater than or equal to (>=)50.0 Kilogram (kg) for males and >=45.0 kg for females.
Female participant of childbearing potential 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 is not of childbearing potential must meet at least one of the following criteria: A. Achieved postmenopausal status, defined as follows: cessation of regular menses for at least 12 consecutive months with no alternative pathological or physiological cause; and have a serum follicle-stimulating hormone (FSH) level >= 40 mili international unit per milliliter (mIU/mL) B. Have undergone a documented (including self-reported) hysterectomy and/or bilateral oophorectomy.

Key exclusion criteria (38 listed)

Participant who is an investigational site staff member directly involved in the conduct of the study and his/her family members, site staff member otherwise supervised by the Investigator, or participant who is a GlaxoSmithKline (GSK) employee directly involved in the conduct of the study.
Participation in other studies involving investigational drug(s) within 30 days prior to study entry and/or during study participation.
Acute or chronic medical or psychiatric 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.
Pregnant female participant as confirmed by a positive pregnancy test or intending to become pregnant over the duration of the study.
Breastfeeding female participant.

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Advil PM Liqui-Gels MinisIbuprofen/diphenhydramine hydrochloride 200 mg/25 mg, Oral capsule which is a size reduction of the currently marketed reference product.	Drug	Advil PM Liqui-Gels Minis
Advil PM Liqui-GelsIbuprofen/diphenhydramine hydrochloride 200 mg/25 mg, Oral capsule.	Drug	Advil PM Liqui-Gels

Primary outcome

Maximum Observed Plasma Concentration (Cmax) for Ibuprofen
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Cmax was defined as maximum observed post-dose plasma concentration for ibuprofen obtained without interpolation. Blood samples were collected at indicated timepoints and pharmacokinetic (PK) analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Cmax for Diphenhydramine
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Cmax was defined as maximum observed post-dose plasma concentration for diphenhydramine obtained without interpolation. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to the Last Measurable Sampling Time Point (t) (AUC [0-t]) for Ibuprofen
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
AUC (0-t) was defined as the area under the plasma concentration versus time curve calculated from time zero to the last measurable sampling time point, (t) using linear up log down trapezoidal method. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
AUC (0-t) for Diphenhydramine
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
AUC (0-t) was defined as the area under the plasma concentration versus time curve calculated from time zero to the last measurable sampling time point, (t) using linear up log down trapezoidal method. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to Infinity (AUC [0-inf]) for Ibuprofen
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity, computed as AUC0-inf = AUC0-t + C(last)/λz where C(last) was the concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.
AUC (0-inf) for Diphenhydramine
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
AUC (0-inf) was defined as area under the plasma concentration versus time curve calculated from time 0 to infinity computed as AUC0-inf = AUC0-t + C(last)/λz where C(last) was the concentration at the last measurable sampling time point and λz was the terminal elimination rate constant. Blood samples were collected at indicated timepoints and PK analysis was performed. Geometric coefficient of variation was not calculated and the arithmetic coefficient of variation (CV%) is being reported.

11 secondary outcomes

Terminal Elimination Rate Constant (λz) for Ibuprofen
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
λz for Diphenhydramine
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Time of the Maximum Observed Post-dose Concentration (Tmax) for Ibuprofen
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Tmax for Diphenhydramine
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
The Elimination Half-life (t1/2) for Ibuprofen
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
t1/2 for Diphenhydramine
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Apparent Volume of Distribution (Vz/F) for Ibuprofen
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Vz/F for Diphenhydramine
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Apparent Total Clearance (CI/F) for Ibuprofen
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
CI/F for Diphenhydramine
Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)
Number of Participants Reporting Ease of Swallowing on 5-Point Ordinal Scale
Time frame: Post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)

Results and safety

Results posted to the registry on 23 Aug 2024, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Sequence AB: Advil PM Liqui-Gels Minis Followed by Advil PM Liqui-Gels	22	22
Sequence BA: Advil PM Liqui-Gels Followed by Advil PM Liqui-Gels Minis	22	22

Primary outcome: Maximum Observed Plasma Concentration (Cmax) for Ibuprofen

Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention). Geometric mean (Geometric Coefficient of Variation). Unit: nanogram per milliliter (ng/mL)

Measure	Treatment A (Test) n = 42	Treatment B (Reference) n = 42
Value	36879.50 (NA)	38875.03 (NA)

Treatment A (Test) vs Treatment B (Reference): Ratio of Geometric Least Square Mean: 95.13 (90% CI 88.31 to 102.47)

Population analysed: PK analysis set included all participants of the PK population who completed both Treatment Periods, and for which the relevant PK parameters (at least one area under the curve \[AUC\] or Cmax) could be derived. The PK population was defined as all randomized participants who had at least one post-dose PK value, and who had no major protocol deviations concerning PKs.

Primary outcome: Cmax for Diphenhydramine

Time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1,1.25,1.5,1.75,2,2.25,2.5,2.75,3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5,6,8,10,12,16,24,36, and 48 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention). Geometric mean (Geometric Coefficient of Variation). Unit: ng/mL

Measure	Treatment A (Test) n = 41	Treatment B (Reference) n = 41
Value	75.40 (NA)	73.22 (NA)

Treatment A (Test) vs Treatment B (Reference): Ratio of Geometric Least Square Mean: 102.51 (90% CI 93.54 to 112.35)

Population analysed: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.

Primary outcome: Area Under the Plasma Concentration Versus Time Curve Calculated From Time 0 to the Last Measurable Sampling Time Point (t) (AUC [0-t]) for Ibuprofen

Measure	Treatment A (Test) n = 42	Treatment B (Reference) n = 42
Value	121612.36 (NA)	123012.43 (NA)

Treatment A (Test) vs Treatment B (Reference): Ratio of Geometric Least Square Mean: 99.15 (90% CI 96.76 to 101.61)

Population analysed: PK analysis set.

Primary outcome: AUC (0-t) for Diphenhydramine

Measure	Treatment A (Test) n = 41	Treatment B (Reference) n = 41
Value	746.76 (NA)	728.13 (NA)

Treatment A (Test) vs Treatment B (Reference): Ratio of Geometric Least Square Mean: 102.62 (90% CI 98.15 to 107.30)

Population analysed: PK analysis set. Here, overall number analyzed is defined as the number of participants with data available for analysis for this outcome measure.

11 secondary outcomes are reported in the full results.

Adverse events

Time frame: From screening up to end of study (up to 38 days). Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Treatment A (Test)	0 of 42 (0%)	3 of 42 (7.1%)	0 of 42
Treatment B (Reference)	0 of 44 (0%)	5 of 44 (11.4%)	0 of 44

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 23 Aug 2024.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Individual participant dataSharing planned: Yes. Anonymized individual participant data and study documents can be requested for further research from ww.clinical-trial-register@haleon.com

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

The record lists no contact. Use the official record to reach the sponsor.

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Advil PM Liqui-Gels Minis and Advil PM Liqui-Gels in people with Pain, run by HALEON at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 38 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 23 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 23 Aug 2024). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Observed Plasma Concentration (Cmax) for Ibuprofen (time frame: 1 hour prior to dosing (pre-dose) and at 10,15,30,45 minutes and 1, 1.25, 1.5, 1.75, 2, 2.25, 2.5, 2.75, 3, 3.25, 3.5, 3.75, 4, 4.25, 4.5, 4.75, 5, 5.25, 5.5, 6, 8,10,12 and 16 hours post-dose on Day 1 (First Intervention) and Day 11 (Second Intervention)). The study lists 6 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05674721.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Aug 2024.