HealthyPhase 1NCT03074162
Comparison of the Bioavailability of Diclofenac in a Combination Product (Diclofenac 2% + Capsaicin 0.075% Topical Gel) With Two Diclofenac Only Products, Diclofenac Mono Gel 2% and Voltarol® 12 Hour Emulgel 2.32% Gel, in Healthy Volunteers
A Phase 1 study testing Diclofenac Sodium, Diclofenac & Capsaicin and Diclofenac Sodium Topical Gel in people with Healthy, run by Boehringer Ingelheim at 1 site in South Africa.
Trial summary
The main objective of this study is to assess the relative systemic bioavailability of diclofenac in the presence and absence of capsaicin by comparing the systemic bioavailability of diclofenac from a combination product (Diclofenac 2% + Capsaicin 0.075% Topical Gel) with two diclofenac only products, Diclofenac Mono… Read more about this study
- Who is it for?
- Ages 18 to 50 years
- Conditions the study is for
- Healthy
- What is being tested?
- Diclofenac Sodium, Diclofenac & Capsaicin and Diclofenac Sodium Topical Gel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 1 siteSouth Africa
- Study dates
- 20 Apr 2017to 29 Jun 2017
- 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 50 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- Healthy males and females, 18 to 50 years (inclusive) at time of screening.
- Body mass index (BMI) between 18.5 and 29.9 kg/m2 (inclusive).
- Body mass not less than 50 kg for males and females.
- Findings for medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be normal or within laboratory reference ranges for the relevant laboratory tests, unless the PI considers the deviation to be not clinically significant for the purpose of the study.
- Non-smokers.
- Females, if:
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- Not of childbearing potential,
- Of childbearing potential, the following conditions are to be met:
- Negative pregnancy test.
- Not lactating.
- Abstaining from sexual activity (if this is the usual lifestyle of the subject) or must agree to use an accepted method of contraception, and agree to continue with the same method throughout the study.
- Written informed consent given for participation in the study.
- Further inclusion criteria apply.
Who cannot join
- Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.
- Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol per week for females. One unit (10 g alcohol) is equal to beer (330 mL), wine (200 mL), or distilled spirits (25 mL) per day.
- Regular exposure to substances of abuse (other than alcohol) within the past year.
- Use of any medication, prescribed or over-the-counter (especially products containing diclofenac or use of other oral nonsteroidal anti-inflammatory drugs [NSAIDS]) or herbal remedies, within 2 weeks before the first administration of Investigational medicinal product (IMP) except if this will not affect the outcome of the study in the opinion of the PI (Principal Investigator) (in collaboration with the Sponsor). In this study the concomitant use of hormonal contraceptives is allowed.
- Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks (or within 5 elimination half-lives for chemical entities or 2 elimination half-lives for anti-bodies or insulin), whichever is the longer before administration of IMP in this study, at the discretion of the PI.
- Treatment within the previous 3 months before the first administration of IMP with any drug with a well-defined potential for adversely affecting a major organ or system.
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- A major illness during the 3 months before commencement of the screening period.
- History of hypersensitivity or allergy (acute rhinitis, angioedema, urticaria or bronchial asthma) to the IMP or its excipients or any related medication (Aspirin or any other NSAID).
- History of hypersensitivity or allergy to cayenne pepper or other capsaicinoids (paprika plants).
- History of bronchospasm or bronchial asthma, arterial hypertension, myocardial infarction, thrombotic events, stroke, congestive heart failure, impaired renal function or liver disease.
- History or current diagnosis of gastrointestinal bleeding or peptic ulcer disease.
- Relevant history or laboratory or clinical findings indicative of acute or chronic disease, likely to influence study outcome.
- Donation or loss of blood equal to or exceeding 500 mL during the 8 weeks before the first administration of IMP (Investigational medicinal product) .
- Bruises, damaged skin, eczema or wounds on the application site, or the application site inappropriate for applying the IMP in the opinion of the PI (Principal Investigator).
- Further exclusion criteria apply.
Trial locations and contacts
1 site in 1 country.
South Africa1 site
Bloemfontein Early Phase Clinical Unit, PAREXEL International (South Africa)
Bloemfontein, 9301
About this study
Official title: A SINGLE CENTER, MULTIPLE DOSE, OPEN-LABEL, RANDOMIZED, THREE-PERIOD CROSSOVER STUDY TO DETERMINE THE RELATIVE BIOAVAILABILITY OF DICLOFENAC IN THE TOPICAL GEL COMBINATION PRODUCT (DICLOFENAC 2% + CAPSAICIN 0.075%) COMPARED TO DICLOFENAC MONO GEL 2% AND VOLTAROL® 12 HOUR EMULGEL 2.32% GEL IN AT LEAST 42 HEALTHY MALES AND FEMALES
The main objective of this study is to assess the relative systemic bioavailability of diclofenac in the presence and absence of capsaicin by comparing the systemic bioavailability of diclofenac from a combination product (Diclofenac 2% + Capsaicin 0.075% Topical Gel) with two diclofenac only products, Diclofenac Mono Gel 2% and Voltarol® 12 Hour Emulgel 2.32% Gel, following topical administration.
In order to examine potential racial differences in pharmacokinetics (PK), the study population will be stratified 50:50, Caucasian versus Black people. With respect to the main objective, additionally a supportive analysis will be performed to investigate the influence of race on the intra-individual bioavailability ratios.
- Conditions
- Healthy
- Being tested
- Diclofenac Sodium, Diclofenac & Capsaicin, Diclofenac Sodium Topical Gel
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Diclofenac SodiumDrug
twice daily
Diclofenac & CapsaicinDrug
twice daily
Diclofenac Sodium Topical GelDrug
twice daily
| Study group | Role | What they receive |
|---|---|---|
| Diclofenac Sodium (A) | Experimental | Not described Receives: Drug: Diclofenac Sodium |
| Diclofenac & Capsaicin (B) | Experimental | Not described Receives: Drug: Diclofenac & Capsaicin |
| Diclofenac Sodium Topical Gel | Active comparator | Not described Receives: Drug: Diclofenac Sodium Topical Gel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7)
AUC0-τ,ss, Area under the plasma concentration-time curve (AUC) over one dosing interval at steady state for diclofenac at day 7 (τ = 12 hours). Stratification by race was analysed using a supportive Analysis of Variance (ANOVA) yielding point estimates for each underlying pairwise comparison analog to the main analysis. As the resulting two Least Square Means and Geometric Means (gMeans) per treatment and race are very similar, only gMeans per treatment and race are presented.
Measured: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7)
Cmax,ss, Maximum plasma of diclofenac concentration during a dosage interval obtained directly from the concentration-time data at steady state for diclofenac on day 7. Stratification by race was analysed using a supportive Analysis of Variance (ANOVA) yielding point estimates for each underlying pairwise comparison analog to the main analysis. As the resulting two Least Square Means and gMeans per treatment and race are very similar, only gMeans per treatment and race are presented.
Measured: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Secondary outcomes (3)
Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7)
tmax,ss, Time to maximum observed plasma concentration at steady state for diclofenac at day 7 (tmax,ss). Descriptive statistics by race are reported in addition.
Measured: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State
Average plasma concentration (Cav,ss) calculated as AUC0-t,ss divided by τ=12 hours (τ is the duration of the dosing interval). Descriptive statistics by race are reported in addition.
Measured: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss]
Percentage peak-trough fluctuation (%PTF) which was calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss] for Diclofenac. Descriptive statistics by race are reported in addition.
Measured: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Mar 2017
- Study start20 Apr 2017
- Primary completion29 Jun 2017
- Study completion29 Jun 2017
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 HealthyStudies of the same condition, open and under way.
- More trials run by Boehringer IngelheimThe 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
- 48 participants (actual)
Sponsor and investigators
- Lead sponsor
- Boehringer Ingelheim
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Boehringer Ingelheim, Study chair, Boehringer Ingelheim
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03074162
- Sponsor's protocol ID
- 1358.2
- Status last verified
- Feb 2019
- First submitted
- 3 Mar 2017
- Last updated
- 1 Mar 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Mar 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A SINGLE CENTER, MULTIPLE DOSE, OPEN-LABEL, RANDOMIZED, THREE-PERIOD CROSSOVER STUDY TO DETERMINE THE RELATIVE BIOAVAILABILITY OF DICLOFENAC IN THE TOPICAL GEL COMBINATION PRODUCT (DICLOFENAC 2% + CAPSAICIN 0.075%) COMPARED TO DICLOFENAC MONO GEL 2% AND VOLTAROL® 12 HOUR EMULGEL 2.32% GEL IN AT LEAST 42 HEALTHY MALES AND FEMALES
- ClinicalTrials.gov ID
- NCT03074162
- Acronym / sponsor ID
- 1358.2
- Conditions
- Healthy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Boehringer IngelheimIndustry (pharma, biotech, devices)
- Study start
- 20 Apr 2017 (actual)
- Primary completion
- 29 Jun 2017 (actual)
- Study completion
- 29 Jun 2017 (actual)
- First posted
- 8 Mar 2017 (actual)
- Results
- Posted 1 Mar 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The main objective of this study is to assess the relative systemic bioavailability of diclofenac in the presence and absence of capsaicin by comparing the systemic bioavailability of diclofenac from a combination product (Diclofenac 2% + Capsaicin 0.075% Topical Gel) with two diclofenac only products, Diclofenac Mono Gel 2% and Voltarol® 12 Hour Emulgel 2.32% Gel, following topical administration.
In order to examine potential racial differences in pharmacokinetics (PK), the study population will be stratified 50:50, Caucasian versus Black people. With respect to the main objective, additionally a supportive analysis will be performed to investigate the influence of race on the intra-individual bioavailability ratios.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Diclofenac Sodium (A) | Experimental | Drug: Diclofenac Sodium |
| Diclofenac & Capsaicin (B) | Experimental | Drug: Diclofenac & Capsaicin |
| Diclofenac Sodium Topical Gel | Active comparator | Drug: Diclofenac Sodium Topical Gel |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (13 listed)
- Healthy males and females, 18 to 50 years (inclusive) at time of screening.
- Body mass index (BMI) between 18.5 and 29.9 kg/m2 (inclusive).
- Body mass not less than 50 kg for males and females.
- Findings for medical history, vital signs, physical examination, standard 12-lead electrocardiogram (ECG) and laboratory investigations must be normal or within laboratory reference ranges for the relevant laboratory tests, unless the PI considers the deviation to be not clinically significant for the purpose of the study.
- Non-smokers.
Key exclusion criteria (15 listed)
- Evidence of psychiatric disorder, antagonistic personality, poor motivation, emotional or intellectual problems likely to limit the validity of consent to participate in the study or limit the ability to comply with protocol requirements.
- Current alcohol use > 21 units of alcohol per week for males and > 14 units of alcohol per week for females. One unit (10 g alcohol) is equal to beer (330 mL), wine (200 mL), or distilled spirits (25 mL) per day.
- Regular exposure to substances of abuse (other than alcohol) within the past year.
- Use of any medication, prescribed or over-the-counter (especially products containing diclofenac or use of other oral nonsteroidal anti-inflammatory drugs [NSAIDS]) or herbal remedies, within 2 weeks before the first administration of Investigational medicinal product (IMP) except if this will not affect the outcome of the study in the opinion of the PI (Principal Investigator) (in collaboration with the Sponsor). In this study the concomitant use of hormonal contraceptives is allowed.
- Participation in another study with an experimental drug, where the last administration of the previous IMP was within 8 weeks (or within 5 elimination half-lives for chemical entities or 2 elimination half-lives for anti-bodies or insulin), whichever is the longer before administration of IMP in this study, at the discretion of the PI.
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 |
|---|---|---|
| Diclofenac Sodiumtwice daily | Drug | Diclofenac Sodium (A) |
| Diclofenac & Capsaicintwice daily | Drug | Diclofenac & Capsaicin (B) |
| Diclofenac Sodium Topical Geltwice daily | Drug | Diclofenac Sodium Topical Gel |
Primary outcome
Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7)
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
AUC0-τ,ss, Area under the plasma concentration-time curve (AUC) over one dosing interval at steady state for diclofenac at day 7 (τ = 12 hours). Stratification by race was analysed using a supportive Analysis of Variance (ANOVA) yielding point estimates for each underlying pairwise comparison analog to the main analysis. As the resulting two Least Square Means and Geometric Means (gMeans) per treatment and race are very similar, only gMeans per treatment and race are presented.
Maximum Plasma Concentration During a Dosage Interval (Cmax,ss) Obtained Directly From the Concentration-time Data for Diclofenac at Steady State (Day 7)
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Cmax,ss, Maximum plasma of diclofenac concentration during a dosage interval obtained directly from the concentration-time data at steady state for diclofenac on day 7. Stratification by race was analysed using a supportive Analysis of Variance (ANOVA) yielding point estimates for each underlying pairwise comparison analog to the main analysis. As the resulting two Least Square Means and gMeans per treatment and race are very similar, only gMeans per treatment and race are presented.
3 secondary outcomes
Time to Maximum Observed Plasma Concentration at Steady State for Diclofenac at Steady State (Tmax,ss) (Day 7)
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Average Plasma Concentration (Cav,ss) for Diclofenac at Steady State
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Percentage Peak-trough Fluctuation (%PTF), Calculated as [100*(Cmax,ss - Cpre,ss)/Cav,ss]
Time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 1 Mar 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink provided by the sponsor.
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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.
Boehringer Ingelheim study chair
Boehringer Ingelheim
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 Diclofenac Sodium, Diclofenac & Capsaicin and Diclofenac Sodium Topical Gel in people with Healthy, run by Boehringer Ingelheim at 1 site in South Africa.
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 13 inclusion and 15 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 1 Mar 2019. 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 South Africa. 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 1 Mar 2019). 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?
Area Under the Plasma Concentration-time Curve (AUC) Over One Dosing Interval for Diclofenac at Steady State (AUC0-τ,ss) (τ = 12 Hours) (Day 7) (time frame: Pharmacokinetic samples were collected on Day 7 at pre-dose and 0.5, 1, 2, 3, 4, 6, 8, 10 and 12 hours after the drug administration). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 1 Mar 2019.