Hepatic ImpairmentPhase 1NCT02286609
A Single Dose Evaluation of the Effects of Moderate Hepatic Impairment on Deflazacort Pharmacokinetics
A Phase 1 study testing Deflazacort in people with Hepatic Impairment, run by PTC Therapeutics at 2 sites in United States.
Trial summary
This is a non-randomized, open-label, single-dose study to compare the PK of 21-desacetyl-DFZ and, if data permits, deflazacort in 8 subjects with moderate hepatic impairment (based on the Child Pugh classification, Grade B) to that of 8 healthy matched control subjects (age, body mass index [BMI], and gender). Read more about this study
- Who is it for?
- Ages 18 to 80 yearsHealthy volunteers can take part
- Conditions the study is for
- Hepatic Impairment
- What is being tested?
- Deflazacort
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 16 participants
- Where
- 2 sitesUnited States
- Study dates
- Dec 2014to Feb 2015
- 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
- All Subjects
- Continuous non-smokers or moderate smokers.
- For a female of non-childbearing potential: must have undergone one a sterilization procedures or be postmenopausal with amenorrhea for at least 1 year prior to dosing 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 dosing until 90 days Subject with Moderate Hepatic Impairment
- Adult male or female, 18 80 years of age
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- BMI ≥ 18.5 and ≤ 40.0 kg/m2
- Subject's score on the Child-Pugh scale must range from 7 to 9 (moderate hepatic insufficiency)
- Subject has a diagnosis of chronic (> 6 months), stable (no acute episodes of illness within the previous 2 months due to deterioration in hepatic function) hepatic insufficiency with features of cirrhosis due to any etiology.
- Healthy Subject
- Healthy adult male and female subjects will be matched 1:1 to a specific subject in the moderate hepatic impairment cohort based upon age, BMI, and gender.
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 hypersensitivity or idiosyncratic reaction to the study drug, related compounds (e.g., steroids or their formulations including lactose and corn starch).
- History (within the last year prior to dosing) or presence of peptic ulcers.
- History or presence of:
- Gastritis or esophagitis, diverticulitis, ulcerative colitis (if there is probability of impending perforation), abscess or pyogenic infections, or fresh intestinal anastomosis;
- Previous corticoids-induced myopathy;
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- Ocular herpes simplex;
- Symptomatic cardiomyopathy at screening;
- Immunosuppression or other contraindications for corticosteroid treatment;
- History of chronic systemic fungal or viral infections;
- Galactose intolerance, Lapp lactose deficiency, or glucose-galactose malabsorption;
- Osteoporosis;
- Myasthenia gravis;
- Epilepsy;
- Idiopathic hypocalcuria.
- Seated blood pressure is less than 90/40 mmHg or greater than 160/95 mmHg
- Seated heart rate is lower than 40 bpm or higher than 99 bpm
- QTcF interval is > 500 msec
- 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 prior to dosing or any oral form of corticoids in 30 days
- Unable to refrain from or anticipates the use of:
- Any drug known to be moderate or strong inhibitors or inducers of cytochrome P450 (CYP) 3A or P-glycoprotein (P-gp) for 14 days or 28 days, respectively
- Any medication or substance, vitamin supplements, natural or herbal supplements which cannot be discontinued at least 14 days
- Female subjects of childbearing potential.
- Female subjects who are pregnant or lactating.
- Positive results at screening for HIV.
- Has 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 Subject with Moderate Hepatic Impairment
- Has history of organ transplant.
- History of drug abuse within the past 2 years
- Has a positive urine drug or urine/breath alcohol testing Healthy Subject
- History or presence of alcoholism or drug abuse within the past 2 years
- Positive urine drug or urine/breath alcohol testing results at screening or check in.
- Positive results at screening for HBsAg or HCV.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
University of Miami Division of Clinical Pharmacology
Miami, Florida, 33136
Orlando Clinical Research Center
Orlando, Florida, 32809
About this study
Official title: A Single Dose Evaluation of the Effects of Moderate (Child-Pugh Grade B) Hepatic Impairment on Deflazacort Pharmacokinetics
This is a non-randomized, open-label, single-dose study to compare the PK of 21-desacetyl-DFZ and, if data permits, deflazacort in 8 subjects with moderate hepatic impairment (based on the Child Pugh classification, Grade B) to that of 8 healthy matched control subjects (age, body mass index [BMI], and gender).
Read the detailed description
This is a non-randomized, open-label, single-dose study to compare the PK of 21-desacetyl-DFZ and, if data permits, deflazacort in 8 subjects with moderate hepatic impairment (based on the Child Pugh classification, Grade B) to that of 8 healthy matched control subjects (age, body mass index [BMI], and gender).
On Day 1, a single oral dose of deflazacort will be administered followed by serial blood sampling for 24 hours to assess the PK of 21-desacetyl-DFZ and, if data permits, deflazacort.
Safety will be monitored throughout the study by repeated clinical and laboratory evaluations.
Subjects will return to the Clinical Research Unit (CRU) 3 days (± 1 day) following study drug administration to determine if any adverse events (AEs) have occurred since the last study visit. Subjects who terminate the study early will be contacted if the Principal Investigator (PI) deems necessary.
A total of sixteen (16) adult male and female subjects will be enrolled. Hepatic Impaired Cohort: Eight (8) subjects with moderate hepatic insufficiency (a score of 7 to 9, on the Child-Pugh scale).
Healthy Match Control Cohort: Eight (8) healthy subjects. Subjects will be matched for age [± 15 years], BMI [± 15 %], and gender [1:1] to the subjects in the moderate hepatic impaired cohort.
- Conditions
- Hepatic Impairment
- Being tested
- Deflazacort
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
DeflazacortDrug
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 immediately to the active metabolite, 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.
| Study group | Role | What they receive |
|---|---|---|
| Hepatic Impairment | Experimental | Eight (8) subjects with moderate hepatic insufficiency (a score of 7 to 9, on the Child-Pugh scale) will receive one 18 mg dose of deflazacort Receives: Drug: Deflazacort |
| Healthy Volunteer | Experimental | Eight (8) healthy subjects. Subjects will be matched for age [± 15 years], BMI [± 15 %], and gender [1:1] to the subjects in the moderate hepatic impaired cohort; will receive 18 mg dose of deflazacort Receives: Drug: Deflazacort |
What is being measured
The primary outcome is the main question the study is designed to answer.
Hepatic impairment on the pharmacokinetics (PK) of deflazacort in subjects with moderate hepatic impairment including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
Hepatic impairment on the pharmacokinetics (PK) of deflazacort in subjects with moderate hepatic impairment including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
Measured: 1 day
Secondary outcomes (1)
Safety and tolerability of one dose of deflazacort in subjects with hepatic impairment as measured by capturing occurrence of adverse events.
Safety and tolerability of one dose of deflazacort in subjects with hepatic impairment as measured by capturing occurrence of adverse events.
Measured: 1 day
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 startDec 2014
- Primary completionFeb 2015
- Study completionFeb 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Hepatic ImpairmentStudies 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
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 16 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
- NCT02286609
- Sponsor's protocol ID
- MP-104-CL-023
- 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 Single Dose Evaluation of the Effects of Moderate (Child-Pugh Grade B) Hepatic Impairment on Deflazacort Pharmacokinetics
- ClinicalTrials.gov ID
- NCT02286609
- Acronym / sponsor ID
- MP-104-CL-023
- Conditions
- Hepatic Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 16 participants (actual)
- Lead sponsor
- PTC TherapeuticsIndustry (pharma, biotech, devices)
- Study start
- Dec 2014
- Primary completion
- Feb 2015 (actual)
- Study completion
- Feb 2015 (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.
This is a non-randomized, open-label, single-dose study to compare the PK of 21-desacetyl-DFZ and, if data permits, deflazacort in 8 subjects with moderate hepatic impairment (based on the Child Pugh classification, Grade B) to that of 8 healthy matched control subjects (age, body mass index [BMI], and gender).
Detailed description
This is a non-randomized, open-label, single-dose study to compare the PK of 21-desacetyl-DFZ and, if data permits, deflazacort in 8 subjects with moderate hepatic impairment (based on the Child Pugh classification, Grade B) to that of 8 healthy matched control subjects (age, body mass index [BMI], and gender).
On Day 1, a single oral dose of deflazacort will be administered followed by serial blood sampling for 24 hours to assess the PK of 21-desacetyl-DFZ and, if data permits, deflazacort.
Safety will be monitored throughout the study by repeated clinical and laboratory evaluations.
Subjects will return to the Clinical Research Unit (CRU) 3 days (± 1 day) following study drug administration to determine if any adverse events (AEs) have occurred since the last study visit. Subjects who terminate the study early will be contacted if the Principal Investigator (PI) deems necessary.
A total of sixteen (16) adult male and female subjects will be enrolled. Hepatic Impaired Cohort: Eight (8) subjects with moderate hepatic insufficiency (a score of 7 to 9, on the Child-Pugh scale).
Healthy Match Control Cohort: Eight (8) healthy subjects. Subjects will be matched for age [± 15 years], BMI [± 15 %], and gender [1:1] to the subjects in the moderate hepatic impaired cohort.
Study design
- Primary purpose
- Basic science
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Hepatic Impairment | Experimental | Drug: DeflazacortEight (8) subjects with moderate hepatic insufficiency (a score of 7 to 9, on the Child-Pugh scale) will receive one 18 mg dose of deflazacort |
| Healthy Volunteer | Experimental | Drug: DeflazacortEight (8) healthy subjects. Subjects will be matched for age [± 15 years], BMI [± 15 %], and gender [1:1] to the subjects in the moderate hepatic impaired cohort; will receive 18 mg dose of deflazacort |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- All Subjects
- Continuous non-smokers or moderate smokers.
- For a female of non-childbearing potential: must have undergone one a sterilization procedures or be postmenopausal with amenorrhea for at least 1 year prior to dosing 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 dosing until 90 days Subject with Moderate Hepatic Impairment
Key exclusion criteria (37 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 hypersensitivity or idiosyncratic reaction to the study drug, related compounds (e.g., steroids or their formulations including lactose and corn starch).
- History (within the last year prior to dosing) or presence of peptic ulcers.
- History or presence of:
- Seated blood pressure is less than 90/40 mmHg or greater than 160/95 mmHg
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 |
|---|---|---|
| DeflazacortAlso: 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 immediately to the active metabolite, 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. | Drug | Healthy Volunteer, Hepatic Impairment |
Primary outcome
Hepatic impairment on the pharmacokinetics (PK) of deflazacort in subjects with moderate hepatic impairment including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration.
Time frame: 1 day
Hepatic impairment on the pharmacokinetics (PK) of deflazacort in subjects with moderate hepatic impairment 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 subjects with hepatic impairment as measured by capturing occurrence of adverse events.
Time frame: 1 day
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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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
2 sites 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 in people with Hepatic Impairment, run by PTC Therapeutics at 2 sites 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 11 inclusion and 37 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 2 sites 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?
Hepatic impairment on the pharmacokinetics (PK) of deflazacort in subjects with moderate hepatic impairment including the area under the plasma concentration time curve, from time 0 to the last measurable non-zero concentration. (time frame: 1 day). 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.