Healthy VolunteersPhase 1NCT02286635
Evaluate Effects of Multiple Doses of Rifampin and Clarithromycin on the Single Dose Pharmacokinetics of Deflazacort
A Phase 1 study testing Deflazacort and rifampin and Deflazacort and Clarithromycin in people with Healthy Volunteers, run by PTC Therapeutics at 1 site in United States.
Trial summary
The primary objective of the study is to determine the potential effects of multiple doses of rifampin and clarithromycin on the single dose pharmacokinetics (PK) of the deflazacort active metabolite (21 desacetyl-DFZ) in healthy adult subjects. Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Healthy Volunteers
- What is being tested?
- Deflazacort and rifampin and Deflazacort and Clarithromycin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 58 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2014to Dec 2014
- 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 80 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- Healthy, adult, male or female, 18 55 years of age
- Continuous non smoker who has not used nicotine containing products for at least 3 months
- Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2
- For a female of non childbearing potential: must have undergone a sterilization procedures or be postmenopausal with amenorrhea for at least 1 year prior to the first dose of study drug and FSH serum levels consistent with postmenopausal status
- A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days
- If male, must agree not to donate sperm from the first dose of study drug until 90 days
Who cannot join
- Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
- History or presence of alcoholism or drug abuse within the past 2 years
- History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (e.g., steroids or their formulations including lactose)
- History or presence of:
- Symptomatic cardiomyopathy at screening
- Immunosuppression or other contraindications for corticosteroid treatment
Show all 36Show fewer
- History of chronic systemic fungal or viral infections
- Galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption
- Diabetes mellitus
- Osteoporosis
- Myasthenia gravis
- Epilepsy
- Idiopathic hypocalcuria
- Hypothyroidism (TSH clinically significant)
- Gastrointestinal issues or ulcers
- Previous corticoids-induced myopathy
- Ocular herpes simplex
- Female subjects of childbearing potential
- Female subjects who are pregnant or lactating
- Positive urine drug or alcohol results
- Positive urine cotinine
- Positive results for HIV, HBsAg or HCV
- Seated blood pressure is less than 90/40 mmHg or greater than 140/90 mmHg
- Seated heart rate is lower than 40 bpm or higher than 99 bpm
- QTc interval is > 430 msec (males) or > 450 msec (females)
- Has received any live or live-attenuated vaccine within 30 days
- Has received any immunosuppressive agents, coal tar, and/or radiation therapies within 30 days
- Has received injectable corticoids in the 12 weeks dose of study drug or any oral form of corticoids in 30 days
- Estimated creatinine clearance < 80 ml/min
- Unable to refrain from or anticipates the use of
- Any drug, including prescription and non prescription medications, as well as herbal remedies known to be significant inhibitors of CYP 3A4 enzymes and/or P gp for 14 days
- Any drugs known to be significant inducers of CYP 3A4 enzymes and/or P gp, including St. John's Wort, for 28 days
- Have been on a diet incompatible with the on study diet within 28 days
- Donation of blood or significant blood loss within 56 days
- Plasma donation within 7 days
- Participation in another clinical trial within 28 days
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Phase 1, Open-Label, 2-Arm, Fixed-Sequence Study to Evaluate the Potential Effects of Multiple Doses of Rifampin (CYP3A4 Inducer) and Clarithromycin (CYP3A4 Inhibitor) on the Single Dose Pharmacokinetics of Deflazacort in Healthy Subjects
The primary objective of the study is to determine the potential effects of multiple doses of rifampin and clarithromycin on the single dose pharmacokinetics (PK) of the deflazacort active metabolite (21 desacetyl-DFZ) in healthy adult subjects.
Read the detailed description
This is an open label, parallel 2-arm, 2-period, fixed-sequence study in 58 healthy adult non-tobacco using male and female subjects divided into 2 cohorts, with 29 subjects in each arm of the study (Cohorts A and B).
Cohort A:
On Day 1 of Period 1 a single oral dose of deflazacort (Treatment A) will be administered followed by PK sampling for 24 hours for 21 desacetyl DFZ and, if data permit, deflazacort.
In Period 2, multiple oral doses of rifampin will be administered once daily (QD) for 10 consecutive days with a single oral dose of deflazacort coadministered on Day 10 (Treatment B). Pharmacokinetic sampling for 21-desacetyl-DFZ and, if data permit, deflazacort will be taken for 24 hours following deflazacort dosing on Day 10. Morning urine collection will be used to measure 6β-hydroxycortisol and free cortisol concentrations on Days 1, 4, 8, and 10 to evaluate the level of cytochrome P450 (CYP) enzyme induction.
Cohort B:
On Day 1 of Period 1 a single oral dose of deflazacort (Treatment C) will be administered followed by PK sampling for 24 hours for 21-desacetyl-DFZ and, if data permit, deflazacort.
In Period 2, multiple oral doses of clarithromycin will be administered twice daily (BID) for 4 consecutive days with a single oral dose of deflazacort coadministered on the morning of Day 4 (Treatment D). Pharmacokinetic sampling for 21 desacetyl-DFZ and, if data permit, deflazacort will be taken for 24 hours following deflazacort dosing on Day 4.
Both Cohorts A and B:
There will be at least 24 hours between the dose in Period 1 and the first dose in Period 2.
Safety will be monitored throughout the study by repeated clinical and laboratory evaluations.
The clinic will attempt to contact subjects using their standard procedures approximately 14 days after the last study drug administration to determine if any adverse events (AEs) have occurred since the last dose of study drug. Subjects who terminate the study early will be contacted if the Principal Investigator (PI) deems necessary.
Cohort A:
Treatments A and B are described as follows:
Treatment A (Period 1): 18 mg deflazacort (3 x 6 mg tablets) at Hour 0 on Day 1, following an overnight fast.
Treatment B (Period 2): 600 mg rifampin (2 x 300 mg capsules) administered at Hour 0 after an overnight fast every 24 hours for 10 days (within ± 1 hour of dosing time on Day 1), with 18 mg deflazacort (3 x 6 mg tablets) coadministered on Day 10.
Cohort B:
Treatments C and D are described as follows:
Treatment C (Period 1): 18 mg deflazacort (3 x 6 mg tablets) at Hour 0 on Day 1, following an overnight fast.
Treatment D (Period 2): 500 mg clarithromycin (1 x 500 mg tablets) administered at Hour 0 and Hour 12, under fasting conditions, approximately every 12 hours, for 4 days (within ± 1 hour of dosing times on Day 1), with 18 mg deflazacort (3 x 6 mg tablets) coadministered at Hour 0 on the morning of Day 4. The final dose of clarithromycin will be given at Hour 12 in the evening of Day 4.
All study drugs in both cohorts will be administered orally with approximately 240 mL of water.
- Conditions
- Healthy Volunteers
- Being tested
- Deflazacort and rifampin, Deflazacort and Clarithromycin
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Deflazacort and rifampinDrug
Also called DFZ
Deflazacort, a glucocorticoid with anti-inflammatory and immunosuppressive effects, is used in treating a variety of diseases. Pharmacologically it is an inactive pro-drug which is metabolized completely and rapidly to the active drug 21-desacetyldeflazacort (21 desacetyl-DFZ). The elimination of this metabolite is primarily via the urine in humans. Its potency is approximately 70 to 90% of prednisone and 6 mg of deflazacort has approximately the same anti-inflammatory potency as 5 mg of prednisolone or prednisone. Rifampin is a potent inducer of drug metabolism by inducing a variety of hepatic and intestinal CYP enzymes, especially CYP3A4. Rifampin is a semi-synthetic antibiotic.
Deflazacort and ClarithromycinDrug
Also called biaxin
Deflazacort, a glucocorticoid with anti-inflammatory and immunosuppressive effects. It is an inactive pro-drug which is metabolized completely and rapidly to the active drug 21 desacetyl-DFZ. The elimination of this metabolite is primarily via the urine in humans. Its potency is approximately 70 to 90% of prednisone. Clarithromycin is a semi-synthetic macrolide antibiotic. Clarithromycin is active in vitro against a variety of aerobic and anaerobic gram-positive and gram-negative bacteria as well as most mycobacterium avium complex (MAC) bacteria. Additionally, the 14-OH clarithromycin metabolite also has clinically significant antimicrobial activity. Clarithromycin is indicated for the treatment of mild to moderate infections such as pharyngitis/tonsillitis.
| Study group | Role | What they receive |
|---|---|---|
| Cohort A Deflazacort and Rifampin | Experimental | Subjects will recieve one 18 mg dose of deflazacort on Day 1, Period 1 and Day 10, Period 2; cohort A. Subjects will receive once daily dosing of rifampin on Day 1, Period 2 through Day 10, Period 2. Receives: Drug: Deflazacort and rifampin |
| Cohort B Deflazacort and Clarithromycin | Experimental | Subjects will recieve one 18 mg dose of deflazacort on Day 1, Period 1 and Day 4, period 2; cohort B. Subjects will receive twice daily dosing of clarithromycin on Day 1, Period 2 through Day 4, Period 2. Receives: Drug: Deflazacort and Clarithromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
Measured: 10 days and 4 days
Secondary outcomes (1)
Safety and tolerability of one dose of deflazacort in healthy subjects receiving CYP3A4 inhibitors and inducers as measured by capturing occurrence of adverse events.
Safety and tolerability of one dose of deflazacort in healthy subjects receiving CYP3A4 inhibitors and inducers as measured by capturing occurrence of adverse events.
Measured: 10 days and 4 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Nov 2014 (estimated)
- Study startNov 2014
- Primary completionDec 2014
- Study completionDec 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Healthy 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
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 58 participants (actual)
Sponsor and investigators
- Lead sponsor
- PTC Therapeutics
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Bioscience Center, Study director, Marathon Pharmaceuticals, LLC
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02286635
- Sponsor's protocol ID
- MP-104-CL-025
- Status last verified
- Aug 2017
- First submitted
- 4 Nov 2014
- Last updated
- 18 Aug 2017
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-Label, 2-Arm, Fixed-Sequence Study to Evaluate the Potential Effects of Multiple Doses of Rifampin (CYP3A4 Inducer) and Clarithromycin (CYP3A4 Inhibitor) on the Single Dose Pharmacokinetics of Deflazacort in Healthy Subjects
- ClinicalTrials.gov ID
- NCT02286635
- Acronym / sponsor ID
- MP-104-CL-025
- Conditions
- Healthy Volunteers
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 58 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Nov 2014
- Primary completion
- Dec 2014 (actual)
- Study completion
- Dec 2014 (actual)
- First posted
- 10 Nov 2014 (estimated)
- 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.
The primary objective of the study is to determine the potential effects of multiple doses of rifampin and clarithromycin on the single dose pharmacokinetics (PK) of the deflazacort active metabolite (21 desacetyl-DFZ) in healthy adult subjects.
Detailed description
This is an open label, parallel 2-arm, 2-period, fixed-sequence study in 58 healthy adult non-tobacco using male and female subjects divided into 2 cohorts, with 29 subjects in each arm of the study (Cohorts A and B).
Cohort A:
On Day 1 of Period 1 a single oral dose of deflazacort (Treatment A) will be administered followed by PK sampling for 24 hours for 21 desacetyl DFZ and, if data permit, deflazacort.
In Period 2, multiple oral doses of rifampin will be administered once daily (QD) for 10 consecutive days with a single oral dose of deflazacort coadministered on Day 10 (Treatment B). Pharmacokinetic sampling for 21-desacetyl-DFZ and, if data permit, deflazacort will be taken for 24 hours following deflazacort dosing on Day 10. Morning urine collection will be used to measure 6β-hydroxycortisol and free cortisol concentrations on Days 1, 4, 8, and 10 to evaluate the level of cytochrome P450 (CYP) enzyme induction.
Cohort B:
On Day 1 of Period 1 a single oral dose of deflazacort (Treatment C) will be administered followed by PK sampling for 24 hours for 21-desacetyl-DFZ and, if data permit, deflazacort.
In Period 2, multiple oral doses of clarithromycin will be administered twice daily (BID) for 4 consecutive days with a single oral dose of deflazacort coadministered on the morning of Day 4 (Treatment D). Pharmacokinetic sampling for 21 desacetyl-DFZ and, if data permit, deflazacort will be taken for 24 hours following deflazacort dosing on Day 4.
Both Cohorts A and B:
There will be at least 24 hours between the dose in Period 1 and the first dose in Period 2.
Safety will be monitored throughout the study by repeated clinical and laboratory evaluations.
The clinic will attempt to contact subjects using their standard procedures approximately 14 days after the last study drug administration to determine if any adverse events (AEs) have occurred since the last dose of study drug. Subjects who terminate the study early will be contacted if the Principal Investigator (PI) deems necessary.
Cohort A:
Treatments A and B are described as follows:
Treatment A (Period 1): 18 mg deflazacort (3 x 6 mg tablets) at Hour 0 on Day 1, following an overnight fast.
Treatment B (Period 2): 600 mg rifampin (2 x 300 mg capsules) administered at Hour 0 after an overnight fast every 24 hours for 10 days (within ± 1 hour of dosing time on Day 1), with 18 mg deflazacort (3 x 6 mg tablets) coadministered on Day 10.
Cohort B:
Treatments C and D are described as follows:
Treatment C (Period 1): 18 mg deflazacort (3 x 6 mg tablets) at Hour 0 on Day 1, following an overnight fast.
Treatment D (Period 2): 500 mg clarithromycin (1 x 500 mg tablets) administered at Hour 0 and Hour 12, under fasting conditions, approximately every 12 hours, for 4 days (within ± 1 hour of dosing times on Day 1), with 18 mg deflazacort (3 x 6 mg tablets) coadministered at Hour 0 on the morning of Day 4. The final dose of clarithromycin will be given at Hour 12 in the evening of Day 4.
All study drugs in both cohorts will be administered orally with approximately 240 mL of water.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort A Deflazacort and Rifampin | Experimental | Drug: Deflazacort and rifampinSubjects will recieve one 18 mg dose of deflazacort on Day 1, Period 1 and Day 10, Period 2; cohort A. Subjects will receive once daily dosing of rifampin on Day 1, Period 2 through Day 10, Period 2. |
| Cohort B Deflazacort and Clarithromycin | Experimental | Drug: Deflazacort and ClarithromycinSubjects will recieve one 18 mg dose of deflazacort on Day 1, Period 1 and Day 4, period 2; cohort B. Subjects will receive twice daily dosing of clarithromycin on Day 1, Period 2 through Day 4, Period 2. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Healthy, adult, male or female, 18 55 years of age
- Continuous non smoker who has not used nicotine containing products for at least 3 months
- Body mass index (BMI) ≥ 18.5 and ≤ 32.0 kg/m2
- For a female of non childbearing potential: must have undergone a sterilization procedures or be postmenopausal with amenorrhea for at least 1 year prior to the first dose of study drug and FSH serum levels consistent with postmenopausal status
- A non vasectomized, male subject must agree to use a condom with spermicide or abstain from sexual intercourse during the study until 90 days
Key exclusion criteria (36 listed)
- Subject is mentally or legally incapacitated or has significant emotional problems at the time of the screening visit or expected during the conduct of the study
- History or presence of alcoholism or drug abuse within the past 2 years
- History or presence of hypersensitivity or idiosyncratic reaction to the study drugs or related compounds (e.g., steroids or their formulations including lactose)
- History or presence of:
- Female subjects of childbearing potential
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 |
|---|---|---|
| Deflazacort and rifampinAlso: DFZDeflazacort, a glucocorticoid with anti-inflammatory and immunosuppressive effects, is used in treating a variety of diseases. Pharmacologically it is an inactive pro-drug which is metabolized completely and rapidly to the active drug 21-desacetyldeflazacort (21 desacetyl-DFZ). The elimination of this metabolite is primarily via the urine in humans. Its potency is approximately 70 to 90% of prednisone and 6 mg of deflazacort has approximately the same anti-inflammatory potency as 5 mg of prednisolone or prednisone. Rifampin is a potent inducer of drug metabolism by inducing a variety of hepatic and intestinal CYP enzymes, especially CYP3A4. Rifampin is a semi-synthetic antibiotic. | Drug | Cohort A Deflazacort and Rifampin |
| Deflazacort and ClarithromycinAlso: biaxinDeflazacort, a glucocorticoid with anti-inflammatory and immunosuppressive effects. It is an inactive pro-drug which is metabolized completely and rapidly to the active drug 21 desacetyl-DFZ. The elimination of this metabolite is primarily via the urine in humans. Its potency is approximately 70 to 90% of prednisone. Clarithromycin is a semi-synthetic macrolide antibiotic. Clarithromycin is active in vitro against a variety of aerobic and anaerobic gram-positive and gram-negative bacteria as well as most mycobacterium avium complex (MAC) bacteria. Additionally, the 14-OH clarithromycin metabolite also has clinically significant antimicrobial activity. Clarithromycin is indicated for the treatment of mild to moderate infections such as pharyngitis/tonsillitis. | Drug | Cohort B Deflazacort and Clarithromycin |
Primary outcome
Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
Time frame: 10 days and 4 days
Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
1 secondary outcome
Safety and tolerability of one dose of deflazacort in healthy subjects receiving CYP3A4 inhibitors and inducers as measured by capturing occurrence of adverse events.
Time frame: 10 days and 4 days
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 18 Aug 2017.
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Screening Protocol
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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.
Bioscience Center study director
Marathon Pharmaceuticals, LLC
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 Deflazacort and rifampin and Deflazacort and Clarithromycin in people with Healthy Volunteers, run by PTC Therapeutics 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 36 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 18 Aug 2017. 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?
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?
Effects of CYP3A4 inhibitors and inducers on the pharmacokinetics (PK) of deflazacort in healthy subjects including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration. (time frame: 10 days and 4 days). 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 18 Aug 2017.