- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04873063
Evaluation of Systemic Bioavailability and Effects on 24-Hour Plasma Cortisol Profile of 6 mg Delivered Once Daily Versus 3 mg Delivered Twice Daily in Healthy Adult Male Volunteers
Explorative Study of the Safety/Tolerability of Beclomethasone Dipropionate Suppositories: Evaluation of Systemic Bioavailability and Effects on 24-Hour Plasma Cortisol Profile of 6 mg Delivered Once Daily Versus 3 mg Delivered Twice Daily in Healthy Adult Male Volunteers
Single-centre, randomized, double-blind, two-period, two-sequence, cross-over 7-day study.
This study is the first safety/tolerability evaluation of a product -suppository formulation containing 6 mg BDP (once daily dosing), a second-generation oral or rectal corticosteroids with high topical anti-inflammatory efficacy in the gut and minimal systemic bioavailability (BA).
BDP is marketed in different pharmaceutical formulations, including 3 mg suppositories, and approved for ulcerative proctosigmoiditis in the first attack or exacerbation phase at the dosage of 3 mg twice a day. For these reasons, a 6 mg suppository (Test - "T" product) is a scale-up of the 3 mg formulation (Reference - "R" product).
For locally-applied-locally acting drug products that result in quantifiable systemic availability due to absorption from the administration site, relative systemic BA is informative for safety, but also with respect to efficacy. Therefore, safety/tolerability of T is evaluated through a comparison to R.
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
Primary objective is the evaluation of systemic safety of T, based on valid surrogate outcomes - systemic BA (relative BA) at the start of treatment (first 24 hours) and after 7 days of continuous treatment; effects on the hypothalamo-pituitary-adrenal axis (HPA) assessed based on 24-hour cortisol profile after 7 days of continuous treatment. This includes identification of subjects with cortisol levels <10 μg/dL at the last sampling point in the 24-hour cortisol profile (08:00 a.m. on Day 8). In such cases, identified subjects will undergo ACTH stimulation test in the morning of Day 9.
Secondary objective is the evaluation of safety/tolerability based on clinical and laboratory adverse events.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Verona, Italy, 37134
- Centro Ricerche Cliniche AOU Integrata di Verona - Policlinico Universitario G.B. Rossi
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Healthy male, aged between 18 and 55 years. Healthy subjects are defined as individuals who are free from clinically significant illness or disease as determined by their medical history, physical examination, laboratory and other (e.g. ECG) tests.
- BMI 19.0 - 29.0 kg/m2;
- Signed and dated written informed consent of the subject to participate in the clinical study;
- The subject is willing to refrain from the use of illicit drugs and alcohol and to adhere to other protocol-stated restrictions while participating in the study;
- The subject is able to understand and comply with the protocol requirements and instructions and is likely to complete the study as planned;
- Non-smoker for at least 3 months.
Exclusion Criteria:
- Subject with a significant abnormality in the past and/or at the Screening that influences the present general health condition and requires pharmacological treatment during the study;
- History of serious allergic diseases, including allergy to medicinal products, which in opinion of the investigator, contraindicates participation to the trial;
- History of diseases of the alimentary tract, liver or kidneys that may influence absorption, distribution and elimination;
- History of average alcohol consumption;
- Hypersensitivity to BDP or study products inactive ingredients;
- Use of any pharmacological treatments (including high dose vitamins, lozenges, herbal and dietary supplements), with the exception of paracetamol ≤ 1 g/daily, within 15 days before the admission to the study Site in the Period 1;
- Use of steroids, anabolic or hormonal therapy within 3 months before the admission to the study Site in the Period 1;
- Laboratory indication of adrenocortical dysfunction;
- Blood loss exceeding 200 ml over the last 4 weeks before the day of Screening;
- Positive results to Sars Cov-2 nasopharyngeal swab;
- Positive results of HBsAg, anti-HCV, anti-HIV tests;
- Blood pressure: systolic >140mmHg or < 90mmHg, diastolic <60 mmHg or >90 mmHg during screening procedures;
- Subject who adhere to a special diet (e.g. low calories, vegetarian etc.);
- Consumption of products containing methylxanthines in the following average quantities: > 3 cups of 200 ml of strong coffee a day;
- Presence of metabolites of illicit drugs (opioids, cannabis) during screening procedures;
- Participation in other clinical trials during the 6 months preceding the study, counting from the day of last product administration.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Other
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Reference/Test
|
BDP 3 mg bid (R product) BDP 6 mg qd (T product)
Other Names:
|
Experimental: Test/Reference
|
BDP 3 mg bid (R product) BDP 6 mg qd (T product)
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics - Cmax, morning;
Time Frame: Day 1 and Day 7 of each Period
|
Peak exposure after the morning dose (Cmax, morning)
|
Day 1 and Day 7 of each Period
|
Pharmacokinetics - Cmax, evening;
Time Frame: Day 1 and Day 7 of each Period
|
Peak exposure after the evening dose (Cmax, evening)
|
Day 1 and Day 7 of each Period
|
Pharmacokinetics - AUC0-24
Time Frame: Day 1 and Day 7 of each Period
|
• Total exposure over 24 hours (AUC0-24)
|
Day 1 and Day 7 of each Period
|
Pharmacokinetics - AUC0-12
Time Frame: Day 1 and Day 7 of each Period
|
• Total exposure during dosing interval - morning (AUC0-12)
|
Day 1 and Day 7 of each Period
|
Pharmacokinetics - AUC12-24
Time Frame: Day 1 and Day 7 of each Period
|
• Total exposure during dosing interval - evening (AUC12-24)
|
Day 1 and Day 7 of each Period
|
HPA-axis: 24-hour plasma cortisol - AUC0-24, cortisol
Time Frame: Baseline and Day 7 of each Period
|
Area under the cortisol level-time curve over 24 hours (AUC0-24, cortisol). AUC will be determined for each subject/treatment at baseline and at Day 7 by the linear trapezoidal rule and ln-transformed. Ln(AUCs) will be used to determine intra-subject difference Day 7 - baseline that will be subject to analysis. |
Baseline and Day 7 of each Period
|
HPA-axis: 24-hour plasma cortisol - AUC0-12, cortisol
Time Frame: Baseline and Day 7 of each Period
|
Area under the cortisol level-time curve over 12 hours after the morning dose (AUC0-12, cortisol). As above. |
Baseline and Day 7 of each Period
|
HPA-axis: 24-hour plasma cortisol - AUC12-24, cortisol
Time Frame: Baseline and Day 7 of each Period
|
Area under the cortisol level-time curve over 12 hours after the evening dose (AUC12-24, cortisol). As above. |
Baseline and Day 7 of each Period
|
HPA-axis: 24-hour plasma cortisol - pAUC2-8, cortisol
Time Frame: Baseline and Day 7 of each Period
|
Partial area under the cortisol level-time curve "covering" 3rd, 4th, 5th, 6th, 7th and 8th hour post morning dose (i.e., between 10:00 and 16:00 hours, that is, between sampling times at 2 and 8 hours post-dose) - a time period during which normal cortisol levels are still relatively high and the strongest suppression after morning dose could be expected (pAUC2-8, cortisol). As above. |
Baseline and Day 7 of each Period
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Pharmacokinetics - trough concentrations
Time Frame: Day 1 and Day 7 of each Period
|
Trough concentrations for R (C12) and T (C24) dosing on Day 1 and Day 7 as well as morning pre-dose (C0)
|
Day 1 and Day 7 of each Period
|
Pharmacokinetics - Cmax morning/AUC0-12 ratio
Time Frame: Day 1 and Day 7 of each Period
|
Ratio of the peak exposure after the morning dose to exposure over the subsequent 12 hours (illustrates absorption rate) (Cmax,morning/AUC0-12)
|
Day 1 and Day 7 of each Period
|
Pharmacokinetics - Tmax, morning
Time Frame: Day 1 and Day 7 of each Period
|
Time to peak exposure after the morning dose (Tmax,morning)
|
Day 1 and Day 7 of each Period
|
Pharmacokinetics - Percent fluctuation (%PTF12)
Time Frame: Day 7 of each Period
|
Day 7 - percent fluctuation over 12 hours after morning dose (%PTF12)
|
Day 7 of each Period
|
Pharmacokinetics - Percent fluctuation (%PTF24)
Time Frame: Day 7 of each Period
|
Day 7 - percent fluctuation over 24 hours (%PTF24)
|
Day 7 of each Period
|
Pharmacokinetics - Accumulation ratio
Time Frame: Day 1 and Day 7 of each Period
|
Accumulation ratio (Cmax,morning Day 7/Day 1; AUC0-24 Day 7/Day 1).
Accumulation ratio will be estimated based on two outcomes: peak exposure after the morning dose (Cmax, morning) and total exposure over 24 hours (AUC0-24).
|
Day 1 and Day 7 of each Period
|
HPA axis - Number (proportion) of subjects with cortisol <10 μg/dL
Time Frame: Day 8 and 9 of each Period
|
ACTH stimulation test results on the morning of Day 9 (first post-dosing day) dichotomized as "normal" or "abnormal"
|
Day 8 and 9 of each Period
|
HPA axis - Number/proportion of subjects with abnormal ACTH stimulation test.
Time Frame: Day 8 and 9 of each Period
|
Number (proportion) of subjects with cortisol levels <10 μg/dL at 08:00 a.m. on Day 8 and number (proportion) of subjects with abnormal ACTH stimulation test results in the morning of Day 9 (should any subject be submitted).
|
Day 8 and 9 of each Period
|
HPA axis - 24-hour cortisol profile
Time Frame: Baseline and Day 7 of each Period
|
24-hour cortisol profile: time-point-by-time-point differences Day 7 vs. baseline
|
Baseline and Day 7 of each Period
|
Other Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety - Adverse Events
Time Frame: From screening to follow up (approximately 59 days)
|
Adverse events reporting
|
From screening to follow up (approximately 59 days)
|
Safety - Laboratory values
Time Frame: At screening, before each period and at follow-up (+21 days after the end of Period 2)
|
Incidence of abnormal laboratory test results (Urinalysis, biochemical and haematological tests performed)
|
At screening, before each period and at follow-up (+21 days after the end of Period 2)
|
Collaborators and Investigators
Sponsor
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- PSC DS BDP-Once 1
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Sharing Supporting Information Type
- Study Protocol
- Informed Consent Form (ICF)
- Clinical Study Report (CSR)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Healthy Adult Male Volunteers
-
Suzhou Zelgen Biopharmaceuticals Co.,LtdCompleted
-
Jiangsu HengRui Medicine Co., Ltd.Active, not recruitingHealthy Adult Male VolunteersChina
-
Sunshine Lake Pharma Co., Ltd.Completed
-
Sunshine Lake Pharma Co., Ltd.Completed
-
Jiangsu HengRui Medicine Co., Ltd.CompletedHealthy Adult Male VolunteersChina
-
Jiangsu HengRui Medicine Co., Ltd.CompletedHealthy Adult Male VolunteersChina
-
Eisai Co., Ltd.Completed
-
Intarcia TherapeuticsCompletedHealthy Adult Male and Female VolunteersNetherlands
-
Jiangsu HengRui Medicine Co., Ltd.UnknownHealthy Adult Male and Female Volunteers
-
Avanir PharmaceuticalsCompletedHealthy Adult Male and Female VolunteersUnited States
Clinical Trials on Beclomethasone dipropionate
-
Teva Branded Pharmaceutical Products R&D, Inc.Completed
-
Adamis Pharmaceuticals CorporationWithdrawn
-
Adamis Pharmaceuticals CorporationWithdrawn
-
Research in Real-Life LtdTeva Branded Pharmaceutical Products R&D, Inc.Completed
-
SoligenixNational Cancer Institute (NCI)Completed
-
Casa Sollievo della Sofferenza IRCCSFondazione SchenaUnknownUlcerative Colitis Chronic MildItaly
-
Research in Real-Life LtdTeva Branded Pharmaceutical Products R&D, Inc.Completed
-
Henry Ford Health SystemCompleted
-
Roswell Park Cancer InstituteCompletedGraft Versus Host DiseaseUnited States
-
GlaxoSmithKlineCompletedRhinitis, Allergic, PerennialUnited States