Healthy Adult Male VolunteersPhase 1NCT04873063
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
A Phase 1 study testing Beclomethasone dipropionate in people with Healthy Adult Male Volunteers, run by SOFAR S.p.A. at 1 site in Italy.
Trial summary
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… Read more about this study
- Who is it for?
- Ages 18 to 55 years, men onlyHealthy volunteers can take part
- Conditions the study is for
- Healthy Adult Male Volunteers
- What is being tested?
- Beclomethasone dipropionate
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 28 participants
- Where
- 1 siteItaly
- Study dates
- 22 Oct 2021to 28 Apr 2022
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Men only
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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.
Who cannot join
- 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;
Show all 16Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
Centro Ricerche Cliniche AOU Integrata di Verona - Policlinico Universitario G.B. Rossi
Verona, 37134
About this study
Official title: 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).
Read more
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.
Read the 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.
- Conditions
- Healthy Adult Male Volunteers
- Being tested
- Beclomethasone dipropionate
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Beclomethasone dipropionateDrug
Also called Beclomethasone 17,21-dipropionate, BDP
BDP 3 mg bid (R product) BDP 6 mg qd (T product)
| Study group | Role | What they receive |
|---|---|---|
| Reference/Test | Experimental | * 3 mg BDP suppositories (R product) delivered twice daily for 7 days
* Washout period (at least 7-day and preferably no more than 9 days)
* 6 mg BDP suppositories (T product) delivered once daily in the morning for 7 days. Matching placebo suppository will be applied rectally once daily in the evening, on same days as the T product. Receives: Drug: Beclomethasone dipropionate |
| Test/Reference | Experimental | * 6 mg BDP suppositories (T product) delivered once daily in the morning for 7 days. Matching placebo suppository will be applied rectally once daily in the evening, on same days as the T product.
* Washout period (at least 7-day and preferably no more than 9 days)
* 3 mg BDP suppositories (R product) delivered twice daily for 7 days Receives: Drug: Beclomethasone dipropionate |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pharmacokinetics - Cmax, morning;
Peak exposure after the morning dose (Cmax, morning)
Measured: Day 1 and Day 7 of each Period
Pharmacokinetics - Cmax, evening;
Peak exposure after the evening dose (Cmax, evening)
Measured: Day 1 and Day 7 of each Period
Pharmacokinetics - AUC0-24
- Total exposure over 24 hours (AUC0-24)
Measured: Day 1 and Day 7 of each Period
Pharmacokinetics - AUC0-12
- Total exposure during dosing interval - morning (AUC0-12)
Measured: Day 1 and Day 7 of each Period
Pharmacokinetics - AUC12-24
- Total exposure during dosing interval - evening (AUC12-24)
Measured: Day 1 and Day 7 of each Period
HPA-axis: 24-hour plasma cortisol - AUC0-24, cortisol
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.
Measured: Baseline and Day 7 of each Period
HPA-axis: 24-hour plasma cortisol - AUC0-12, cortisol
Area under the cortisol level-time curve over 12 hours after the morning dose (AUC0-12, cortisol).
As above.
Measured: Baseline and Day 7 of each Period
HPA-axis: 24-hour plasma cortisol - AUC12-24, cortisol
Area under the cortisol level-time curve over 12 hours after the evening dose (AUC12-24, cortisol).
As above.
Measured: Baseline and Day 7 of each Period
HPA-axis: 24-hour plasma cortisol - pAUC2-8, cortisol
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.
Measured: Baseline and Day 7 of each Period
Secondary outcomes (9)
Pharmacokinetics - trough concentrations
Trough concentrations for R (C12) and T (C24) dosing on Day 1 and Day 7 as well as morning pre-dose (C0)
Measured: Day 1 and Day 7 of each Period
Pharmacokinetics - Cmax morning/AUC0-12 ratio
Ratio of the peak exposure after the morning dose to exposure over the subsequent 12 hours (illustrates absorption rate) (Cmax,morning/AUC0-12)
Measured: Day 1 and Day 7 of each Period
Pharmacokinetics - Tmax, morning
Time to peak exposure after the morning dose (Tmax,morning)
Measured: Day 1 and Day 7 of each Period
Pharmacokinetics - Percent fluctuation (%PTF12)
Day 7 - percent fluctuation over 12 hours after morning dose (%PTF12)
Measured: Day 7 of each Period
Pharmacokinetics - Percent fluctuation (%PTF24)
Day 7 - percent fluctuation over 24 hours (%PTF24)
Measured: Day 7 of each Period
Pharmacokinetics - Accumulation ratio
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).
Measured: Day 1 and Day 7 of each Period
HPA axis - Number (proportion) of subjects with cortisol <10 μg/dL
ACTH stimulation test results on the morning of Day 9 (first post-dosing day) dichotomized as "normal" or "abnormal"
Measured: Day 8 and 9 of each Period
HPA axis - Number/proportion of subjects with abnormal ACTH stimulation test.
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).
Measured: Day 8 and 9 of each Period
HPA axis - 24-hour cortisol profile
24-hour cortisol profile: time-point-by-time-point differences Day 7 vs. baseline
Measured: Baseline and Day 7 of each Period
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 May 2021
- Study start22 Oct 2021
- Primary completion28 Apr 2022
- Study completion28 Apr 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy Adult Male VolunteersStudies of the same condition, open and under way.
- 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
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Single-centre, randomized, double-blind, two-period, two-sequence, cross-over 7-day study.
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 28 participants (actual)
Sponsor and investigators
- Lead sponsor
- SOFAR S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04873063
- Sponsor's protocol ID
- PSC DS BDP-Once 1
- Status last verified
- May 2022
- First submitted
- 26 Apr 2021
- Last updated
- 4 May 2022
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 4 May 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT04873063
- Acronym / sponsor ID
- PSC DS BDP-Once 1
- Conditions
- Healthy Adult Male Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 28 participants (actual)
- Lead sponsor
- SOFAR S.p.A.Industry (pharma, biotech, devices)
- Study start
- 22 Oct 2021 (actual)
- Primary completion
- 28 Apr 2022 (actual)
- Study completion
- 28 Apr 2022 (actual)
- First posted
- 5 May 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
- Model description
- Single-centre, randomized, double-blind, two-period, two-sequence, cross-over 7-day study.
| Arm | Type | Receives |
|---|---|---|
| Reference/Test | Experimental | Drug: Beclomethasone dipropionate* 3 mg BDP suppositories (R product) delivered twice daily for 7 days * Washout period (at least 7-day and preferably no more than 9 days) * 6 mg BDP suppositories (T product) delivered once daily in the morning for 7 days. Matching placebo suppository will be applied rectally once daily in the evening, on same days as the T product. |
| Test/Reference | Experimental | Drug: Beclomethasone dipropionate* 6 mg BDP suppositories (T product) delivered once daily in the morning for 7 days. Matching placebo suppository will be applied rectally once daily in the evening, on same days as the T product. * Washout period (at least 7-day and preferably no more than 9 days) * 3 mg BDP suppositories (R product) delivered twice daily for 7 days |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- Male only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 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;
Key exclusion criteria (16 listed)
- 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;
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 |
|---|---|---|
| Beclomethasone dipropionateAlso: Beclomethasone 17,21-dipropionate, BDPBDP 3 mg bid (R product) BDP 6 mg qd (T product) | Drug | Reference/Test, Test/Reference |
Primary outcome
Pharmacokinetics - Cmax, morning;
Time frame: Day 1 and Day 7 of each Period
Peak exposure after the morning dose (Cmax, morning)
Pharmacokinetics - Cmax, evening;
Time frame: Day 1 and Day 7 of each Period
Peak exposure after the evening dose (Cmax, evening)
Pharmacokinetics - AUC0-24
Time frame: Day 1 and Day 7 of each Period
• Total exposure over 24 hours (AUC0-24)
Pharmacokinetics - AUC0-12
Time frame: Day 1 and Day 7 of each Period
• Total exposure during dosing interval - morning (AUC0-12)
Pharmacokinetics - AUC12-24
Time frame: Day 1 and Day 7 of each Period
• Total exposure during dosing interval - evening (AUC12-24)
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.
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.
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.
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.
9 secondary outcomes
Pharmacokinetics - trough concentrations
Time frame: Day 1 and Day 7 of each Period
Pharmacokinetics - Cmax morning/AUC0-12 ratio
Time frame: Day 1 and Day 7 of each Period
Pharmacokinetics - Tmax, morning
Time frame: Day 1 and Day 7 of each Period
Pharmacokinetics - Percent fluctuation (%PTF12)
Time frame: Day 7 of each Period
Pharmacokinetics - Percent fluctuation (%PTF24)
Time frame: Day 7 of each Period
Pharmacokinetics - Accumulation ratio
Time frame: 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
HPA axis - Number/proportion of subjects with abnormal ACTH stimulation test.
Time frame: Day 8 and 9 of each Period
HPA axis - 24-hour cortisol profile
Time frame: Baseline and Day 7 of each Period
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 May 2022.
- Individual participant dataSharing planned: Yes
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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 Beclomethasone dipropionate in people with Healthy Adult Male Volunteers, run by SOFAR S.p.A. at 1 site in Italy.
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 16 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 4 May 2022. 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 Italy. 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?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Pharmacokinetics - Cmax, morning; (time frame: Day 1 and Day 7 of each Period). The study lists 9 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 4 May 2022.