Renal ImpairmentPhase 1NCT04446507
A Pharmacokinetic Study of Saroglitazar Magnesium in Subjects with Severe Renal Impairment and Normal Renal Function
A Phase 1 study testing Saroglitazar magnesium in people with Renal Impairment, run by Zydus Therapeutics Inc. at 2 sites in United States.
Trial summary
This will be a Phase 1, Open-label Study of Participants with Normal Renal Function and Participants with Sever Renal Impairment. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Renal Impairment
- What is being tested?
- Saroglitazar magnesium
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 2 sitesUnited States
- Study dates
- 27 Jul 2020to 28 May 2024
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Ability to comprehend and willingness to sign a written ICF for the study.
- Male or female subjects aged 18 to 80 years (inclusive) at the time of signing the ICF.
- Participants will be classified at screening by renal function as determined by the modification of diet in renal disease (MDRD) formula for estimated glomerular filtration rate (eGFR) in subjects with chronic kidney disease (CKD). Classification will be repeated at Day -1, if the renal function classification for the participant is not the same at the two time points, enrollment of the participant will be based on eGFR at screening.
- Group 2 (Normal renal function) subjects, should be in good health as determined by no clinically significant deviations from normal for medical history, physical examination, vital signs, 12 lead electrocardiograms (ECGs), or laboratory examinations at screening or Day-1.
- Group 1 (Severe renal impairment not on HD, eGFR <30) subjects, may have medical findings consistent with their degree of renal impairment, as determined by medical history, physical examination, vital signs, ECGs, and clinical laboratory examinations at screening and Day -1. Participants are eligible if abnormal findings are considered not clinically significant by the Investigator.
- Body mass index within the range 18.0 to 48.0 kg/m2 (inclusive) at screening.
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- Females must be non-pregnant, non-lactating and of non-childbearing potential or using highly efficient contraception for the full duration of the study. Female of childbearing potential and Males must agree to use contraception for the full duration of the study.
- Ability to swallow and retain oral medication.
- Laboratory test values within normal limits or considered not clinically significant by the investigator for subjects in Group 2 with normal renal function. Must have eGFR ≥ 90 by MDRD calculation. To match the older population ranging from 65 years and above in the control group, the eGFR requirement can be set to 70 or above (by MDRD formula) without any signs of kidney damage (like proteinuria) and are otherwise healthy as per the investigator's discretion.
- Group 2 patients with normal renal function must match in age (± 10 years), sex, and weight (± 20 kg) with severe renal impairment participants in the Group 1.
- Laboratory test values for severe renal impairment subjects must be clinically acceptable to the Investigator and meet all of the following parameters at screening:
- ALT value ≤ 3 × ULN
- AST value ≤ 3 × ULN
- Absolute neutrophil count (ANC) ≥ 750/mm3
- Platelets ≥ 50,000/mm3
Who cannot join
- Any significant, unstable medical condition or other instability that would prevent the subject from participating in the study as determined by the investigator or designee.
- History of malignancy of any type in the last 3 years of screening, with the exception of the following: in situ cervical or breast cancer or surgically excised non-melanoma skin cancers (i.e. basal cell or squamous cell carcinoma).
- History of stomach or intestinal surgery or resection within the six months prior to screening that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed).
- History of any significant drug allergy (such as anaphylaxis) deemed clinically relevant by the investigator.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of asymptomatic gallstones) or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
- Any major surgery within 3 months of screening.
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- Donation of blood or blood products within 3 months prior to screening.
- Blood transfusion within 2 weeks of Day -1.
- Current active infectious disease requiring systemic antibiotic, antifungal, or antiviral treatment.
- Use or intend to use any medications/products known to alter drug absorption, metabolism, or elimination processes, including St. John's Wort, within 21 days prior to screening, unless deemed acceptable by the Investigator.
- Receiving or has received any investigational drug within the 30 days or 5 halflives (whichever is longer), before receiving Saroglitazar Magnesium.
- Group 2 (Normal renal function) subjects, who have a history of renal disease or renal injury as indicated by an abnormal BUN or creatinine at screening or Day-1.
- Group 1 (Severe renal impairment) subjects, who have had a change in renal disease status within 30 days of screening, as documented by the participant's medical history and deemed clinically significant by the investigator.
- For healthy renal function subjects, QT interval corrected for heart rate using Fridericia's method (QTcF) > 450 msec, confirmed by repeat measurement. In renal impaired subjects QTcF > 500 msec, confirmed by repeat measurement; no second or third degree AV block.
- Group 1 subjects, who use or intend to use any over-the-counter (vitamins, minerals, and phytotherapeutic/herbal/plant-derived preparations) or prescription medications within 30 days or 5 half-lives (whichever is longer) prior to enrollment, with the exception of hormone replacement therapy and therapies for renal disease and treatments of associated disorders that have been stable for at least 30 days prior to screening and until Day 1, unless deemed acceptable by the investigator (or designee).
- Group 2 Subjects who have taken any prescription medications or over-the counter medications, including herbal products, within 14 days prior to start of study drug dosing, with the exception of vitamins, acetaminophen, hormonal contraceptive medications and/or any other over-the-counter product approved by the investigator.
- Positive alcohol breath test at the time of check-in or those subjects who have current alcohol or substance abuse judged by the investigator to potentially interfere with subject compliance or subject safety.
- Positive test for drugs of abuse at screening or admission, if not accounted by a prescription medication. Subjects with a positive test based on a prescribed medication may be enrolled.
- Any subject with poor peripheral venous access.
- Human immunodeficiency virus (HIV) type 1 antibody, HBsAg or HCV-Ab positive at screening.
- Additional exclusion criteria for Severe Renal Impairment subjects:
- History of nephrectomy or renal transplant
- Any type of dialysis within 3 months prior to screening
- Electrolyte abnormality or other screening laboratory value deemed clinically significant by investigator.
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Zydus US003
DeLand, Florida, 32720
Zydus US001
San Antonio, Texas, 78215
About this study
Official title: A Phase 1, Open-label Study to Evaluate the Pharmacokinetics and Safety of Saroglitazar Magnesium in Participants with Normal Renal Function and Participants with Severe Renal Impairment.
This will be a Phase 1, Open-label Study of Participants with Normal Renal Function and Participants with Sever Renal Impairment.
Read the detailed description
A total of 32 participants will be enrolled:
Group 1 (Severe renal impairment not on HD, eGFR <30) - 16 subjects Subjects will be enrolled and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by another 8 subjects who will receive 4 mg dose).
Group 2 (Normal renal function eGFR ≥90) - 16 subjects Subjects in this group will be matched according to age (± 10 years), sex, and weight (± 20 kg) with participants in Group 1 (Severe renal impairment not on HD) on a one to one basis based on demographic characteristic. In this group, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium.
To match the older population ranging from 65 years and above in the control group, the eGFR requirement can be set to 70 or above (by MDRD formula) without any signs of kidney damage (like proteinuria) and are otherwise healthy as per the investigator's discretion
- Conditions
- Renal Impairment
- Being tested
- Saroglitazar magnesium
- Medical subject headings
- Renal Insufficiency
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Saroglitazar magnesiumDrug
Also called not any
1 dose of 2mg and 4 mg Saroglitazar magnesium will be given to subjects on Day 1
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | Experimental | Subjects in severe renal impairment group will be enrolled and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by another 8 subjects who will receive 4 mg dose). Receives: Drug: Saroglitazar magnesium |
| Group 2 | Experimental | Subjects (Normal renal function eGFR ≥90) will be matched according to age (± 10 years), sex, and weight (± 20 kg) with participants in Group 1 (Severe renal impairment not on HD) on a one to one basis based on demographic characteristic. Here, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium. Receives: Drug: Saroglitazar magnesium |
What is being measured
The primary outcome is the main question the study is designed to answer.
AUC from time zero to infinity (AUC0-∞)
The area under the plasma concentration versus time curve from zero to infinity will be calculated by adding Ct/Kel to AUCt, where Ct is the last quantifiable concentration and Kel is the elimination rate constant.
Measured: Before dosing on Day 1 through Day 7
AUC from time zero to the last quantifiable concentration (AUC0-t)
The area under the plasma concentration versus time curve will be calculated using the linear trapezoidal rule from the zero time point to the last quantifiable concentration.
Measured: Before dosing on Day 1 through Day 7
Cmax
Maximum measured plasma concentration over the time span specified.
Measured: Before dosing on Day 1 through Day 7
Tmax
Time of the maximum measured plasma concentration.
Measured: Before dosing on Day 1 through Day 7
t1/2
The half-life will be calculated by the equation tHalf = 0.693/ Kel. Kel (The terminal elimination rate constant) will be obtained from the slope of the line, fitted by linear least squares regression, through the terminal points of the natural log of the concentration versus time plot for these points
Measured: Before dosing on Day 1 through Day 7
CL/F
Clearance
Measured: Before dosing on Day 1 through Day 7
Vz/F
Volume of distribution
Measured: Before dosing on Day 1 through Day 7
Secondary outcomes (4)
Urine Pharmacokinetic: Ae
Amount of drug excreted during each collection interval
Measured: Before dosing on Day 1 through Day 5
Incidence of AEs
Incidence and severity of AEs as a measure of safety and tolerability will be measured and reported.
Measured: Before dosing on Day 1 through Day 12
Unbound Fraction
Unbound fraction in plasma of Saroglitazar
Measured: Day 1
Unbound concentration
Unbound concentration in plasma of Saroglitazar
Measured: Day 1
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2020
- Study start27 Jul 2020
- Primary completion28 May 2024
- Study completion28 May 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal 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
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- Zydus Therapeutics Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Deven Parmar, MD, Study director, Zydus Therapeutics Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04446507
- Sponsor's protocol ID
- SARO.19.004
- Status last verified
- May 2024
- First submitted
- 15 Jun 2020
- Last updated
- 20 Sep 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1, Open-label Study to Evaluate the Pharmacokinetics and Safety of Saroglitazar Magnesium in Participants with Normal Renal Function and Participants with Severe Renal Impairment.
- ClinicalTrials.gov ID
- NCT04446507
- Acronym / sponsor ID
- SARO.19.004
- Conditions
- Renal Impairment
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- Zydus Therapeutics Inc.Industry (pharma, biotech, devices)
- Study start
- 27 Jul 2020 (actual)
- Primary completion
- 28 May 2024 (actual)
- Study completion
- 28 May 2024 (actual)
- First posted
- 25 Jun 2020 (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.
This will be a Phase 1, Open-label Study of Participants with Normal Renal Function and Participants with Sever Renal Impairment.
Detailed description
A total of 32 participants will be enrolled:
Group 1 (Severe renal impairment not on HD, eGFR <30) - 16 subjects Subjects will be enrolled and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by another 8 subjects who will receive 4 mg dose).
Group 2 (Normal renal function eGFR ≥90) - 16 subjects Subjects in this group will be matched according to age (± 10 years), sex, and weight (± 20 kg) with participants in Group 1 (Severe renal impairment not on HD) on a one to one basis based on demographic characteristic. In this group, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium.
To match the older population ranging from 65 years and above in the control group, the eGFR requirement can be set to 70 or above (by MDRD formula) without any signs of kidney damage (like proteinuria) and are otherwise healthy as per the investigator's discretion
Study design
- Primary purpose
- Other
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Group 1 | Experimental | Drug: Saroglitazar magnesiumSubjects in severe renal impairment group will be enrolled and dosed consecutively (i.e. first 8 subjects of group 1 will receive 2 mg dose, followed by another 8 subjects who will receive 4 mg dose). |
| Group 2 | Experimental | Drug: Saroglitazar magnesiumSubjects (Normal renal function eGFR ≥90) will be matched according to age (± 10 years), sex, and weight (± 20 kg) with participants in Group 1 (Severe renal impairment not on HD) on a one to one basis based on demographic characteristic. Here, 8 participants will be administered single dose of 2 mg Saroglitazar Magnesium and 8 participants will be administered single dose of 4 mg Saroglitazar Magnesium. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Ability to comprehend and willingness to sign a written ICF for the study.
- Male or female subjects aged 18 to 80 years (inclusive) at the time of signing the ICF.
- Participants will be classified at screening by renal function as determined by the modification of diet in renal disease (MDRD) formula for estimated glomerular filtration rate (eGFR) in subjects with chronic kidney disease (CKD). Classification will be repeated at Day -1, if the renal function classification for the participant is not the same at the two time points, enrollment of the participant will be based on eGFR at screening.
- Group 2 (Normal renal function) subjects, should be in good health as determined by no clinically significant deviations from normal for medical history, physical examination, vital signs, 12 lead electrocardiograms (ECGs), or laboratory examinations at screening or Day-1.
- Group 1 (Severe renal impairment not on HD, eGFR <30) subjects, may have medical findings consistent with their degree of renal impairment, as determined by medical history, physical examination, vital signs, ECGs, and clinical laboratory examinations at screening and Day -1. Participants are eligible if abnormal findings are considered not clinically significant by the Investigator.
Key exclusion criteria (24 listed)
- Any significant, unstable medical condition or other instability that would prevent the subject from participating in the study as determined by the investigator or designee.
- History of malignancy of any type in the last 3 years of screening, with the exception of the following: in situ cervical or breast cancer or surgically excised non-melanoma skin cancers (i.e. basal cell or squamous cell carcinoma).
- History of stomach or intestinal surgery or resection within the six months prior to screening that would potentially alter absorption and/or excretion of orally administered drugs (uncomplicated appendectomy, cholecystectomy, and hernia repair will be allowed).
- History of any significant drug allergy (such as anaphylaxis) deemed clinically relevant by the investigator.
- Current or chronic history of liver disease, or known hepatic or biliary abnormalities (with the exception of asymptomatic gallstones) or other hepatic abnormalities that in the opinion of the investigator would preclude the subject from participation in the study.
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 |
|---|---|---|
| Saroglitazar magnesiumAlso: not any1 dose of 2mg and 4 mg Saroglitazar magnesium will be given to subjects on Day 1 | Drug | Group 1, Group 2 |
Primary outcome
AUC from time zero to infinity (AUC0-∞)
Time frame: Before dosing on Day 1 through Day 7
The area under the plasma concentration versus time curve from zero to infinity will be calculated by adding Ct/Kel to AUCt, where Ct is the last quantifiable concentration and Kel is the elimination rate constant.
AUC from time zero to the last quantifiable concentration (AUC0-t)
Time frame: Before dosing on Day 1 through Day 7
The area under the plasma concentration versus time curve will be calculated using the linear trapezoidal rule from the zero time point to the last quantifiable concentration.
Cmax
Time frame: Before dosing on Day 1 through Day 7
Maximum measured plasma concentration over the time span specified.
Tmax
Time frame: Before dosing on Day 1 through Day 7
Time of the maximum measured plasma concentration.
t1/2
Time frame: Before dosing on Day 1 through Day 7
The half-life will be calculated by the equation tHalf = 0.693/ Kel. Kel (The terminal elimination rate constant) will be obtained from the slope of the line, fitted by linear least squares regression, through the terminal points of the natural log of the concentration versus time plot for these points
CL/F
Time frame: Before dosing on Day 1 through Day 7
Clearance
Vz/F
Time frame: Before dosing on Day 1 through Day 7
Volume of distribution
4 secondary outcomes
Urine Pharmacokinetic: Ae
Time frame: Before dosing on Day 1 through Day 5
Incidence of AEs
Time frame: Before dosing on Day 1 through Day 12
Unbound Fraction
Time frame: Day 1
Unbound concentration
Time frame: Day 1
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 20 Sep 2024.
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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.
Deven Parmar, MD study director
Zydus Therapeutics Inc.
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 Saroglitazar magnesium in people with Renal Impairment, run by Zydus Therapeutics Inc. 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 15 inclusion and 24 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 20 Sep 2024. 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?
AUC from time zero to infinity (AUC0-∞) (time frame: Before dosing on Day 1 through Day 7). The study lists 7 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 20 Sep 2024.