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A Phase 1 Study to Evaluate the Pharmacokinetics of Setmelanotide in Subjects With Varying Degrees of Renal Impairment

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ClinicalTrials.gov Identifier: NCT04348175
Recruitment Status : Recruiting
First Posted : April 16, 2020
Last Update Posted : December 31, 2020
Sponsor:
Information provided by (Responsible Party):
Rhythm Pharmaceuticals, Inc.

Brief Summary:

This Phase 1, multi-center, study will enroll patients with renal insufficiency. Single ascending doses of setmelanotide will be evaluated, in semi-sequential group design. The following four cohorts of patients will be evaluated:

Cohort A: setmelanotide in subjects with mild renal insufficiency Cohort B: setmelanotide in subjects with moderate renal insufficiency Cohort C: setmelanotide in subjects with severe renal insufficiency Cohort D: setmelanotide in subjects with normal renal function

All subcutaneous doses will be administered to the abdominal region. Each dose will be studied in a separate cohort of subjects. Cohorts A and B will be performed in a parallel manner. After cohorts A and B have been studied and before subsequent cohort C is dosed, the available safety data (adverse events [AEs], clinical laboratory test results, vital signs and electrocardiograms) from the preceding cohort(s) will be reviewed. In addition, a 48h pause to evaluate safety will be implemented following the enrollment of the first 2 (two) patients in cohort C before treating the remaining patients in the cohort. Cohort D will be performed sequentially following cohort C. Depending on the safety data from the preceding cohort(s), a cohort may be repeated, or the dose may be reduced for future cohorts.


Condition or disease Intervention/treatment Phase
Renal Insufficiency Drug: Setmelanotide Phase 1

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 32 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: A Phase 1, Open-Label, Single-Dose Study to Evaluate the Pharmacokinetics of Setmelanotide in Subjects With Varying Degrees of Renal Impairment
Actual Study Start Date : July 9, 2020
Estimated Primary Completion Date : March 10, 2021
Estimated Study Completion Date : March 10, 2021

Arm Intervention/treatment
Experimental: Mild impairment Drug: Setmelanotide
Setmelanotide will be administered as a single SC dose of 2.0 mg on Day 1. A dose higher than 2.0 mg will not be used during the study.

Experimental: Moderate impairment Drug: Setmelanotide
Setmelanotide will be administered as a single SC dose of 2.0 mg on Day 1. A dose higher than 2.0 mg will not be used during the study.

Experimental: Severe impairment Drug: Setmelanotide
Setmelanotide will be administered as a single SC dose of 2.0 mg on Day 1. A dose higher than 2.0 mg will not be used during the study.

Experimental: Normal (control) Drug: Setmelanotide
Setmelanotide will be administered as a single SC dose of 2.0 mg on Day 1. A dose higher than 2.0 mg will not be used during the study.




Primary Outcome Measures :
  1. Pharmacokinetic Parameter - Peak Plasma Concentration (Cmax) [ Time Frame: 5 days ]
    The primary objective of this study is to evaluate the PK of a single dose of Setmelanotide administered SC in subjects with varying degrees of renal impairment and that of healthy matched control subjects.

  2. Pharmacokinetic Parameter - Area under the plasma concentration versus time curve (AUC) [ Time Frame: 5 days ]
    The primary objective of this study is to evaluate the PK of a single dose of Setmelanotide administered SC in subjects with varying degrees of renal impairment and that of healthy matched control subjects.


Secondary Outcome Measures :
  1. Number of Participants with Abnormal Laboratory Values and/or Adverse Events That Are Related to Treatment [ Time Frame: 5 days ]
    The secondary objective of this study is to evaluate the safety and tolerability of a single dose of Setmelanotide administered SC in subjects with varying degrees of renal impairment.

  2. Number of Participants with Abnormal Vital Sign Findings [ Time Frame: 5 days ]
    Vital signs will include systolic and diastolic blood pressure, pulse rate, respiratory rate, and body temperature.

  3. Number of subjects with Abnormal Electrocardiogram (ECG) findings [ Time Frame: 5 days ]
    Electrocardiogram assessments will include comments on whether the tracings are normal or abnormal, rhythm, presence of arrhythmia or conduction defects, wave morphology, any evidence of myocardial infarction, or ST-segment, T-Wave, and U Wave abnormalities.

  4. Number of subjects with Abnormal Findings in Physical Examination [ Time Frame: 5 days ]
    A full physical examination will include, at minimum, assessment of skin, head, ears, eyes, nose, throat, neck, thyroid, lungs, heart, cardiovascular, abdomen, lymph nodes, and musculoskeletal system/extremities.



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Ages Eligible for Study:   18 Years to 79 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  1. The subject is male or female 18 to 79 years of age, inclusive.
  2. The subject has a BMI of 22 to 35 kg/m2, inclusive, at screening.
  3. Female subjects of childbearing potential must use an acceptable method of birth control (ie, diaphragm with spermicide, intrauterine device, condom with foam or vaginal spermicide, oral contraceptives, or abstinence) or be surgically sterile (ie, hysterectomy, bilateral tubal ligation or bilateral oophorectomy), or postmenopausal (defined as amenorrhea 12 consecutive months and documented plasma follicle-stimulating hormone level in the postmenopausal range according to the laboratory used). Female subjects must have a negative pregnancy test at screening and before the first dose of study drug and must not be lactating. Male subjects with female partners of childbearing potential must be vasectomized, be willing to use an acceptable method of birth control, or practice abstinence during the study. Male subjects must not donate sperm during and for 90 days following their participation in the study.
  4. The subject agrees to comply with all protocol requirements.
  5. The subject is able to provide written informed consent.

    Additional Inclusion Criteria for Subjects with Renal Impairment Only (Cohorts A, B, and C):

  6. The subject has mild, moderate, or severe renal impairment as determined by eGFR and calculated using the MDRD formula.
  7. The subject's renal insufficiency or other related concomitant medical conditions (eg, hypertension, diabetes, anemia) have remained stable for at least 3 months before study drug dosing.
  8. The subject has a resting blood pressure of 90 to 165 mm Hg (systolic) and 45 to 100 mm Hg (diastolic). Measurement can be repeated if the subject has an elevated value that is not consistent with previous history.
  9. The subject has a QTcF of <500 msec.
  10. The subject is judged by the investigator to be in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12-lead ECG results, and physical examination findings, except for findings that, as judged by the investigator, are consistent with the subject's renal impairment or other stable concomitant medical conditions.

    Additional Inclusion Criteria for Healthy Subjects Only (Cohort D):

  11. The subject has normal renal function (≥90 mL/min) as determined by eGFR calculated using the MDRD formula.
  12. The subject will be "matched" to previous Cohorts A, B, and C with regards to age, sex, and BMI characteristics. Each subject in Cohort D will be within 20% of the median age and BMI of the combined median age and BMI across Cohorts A, B, and C.
  13. The subject has a resting blood pressure of 90 to 150 mm Hg (systolic) and 40 to 100 mm Hg (diastolic).
  14. The subject is judged by the investigator to be in good general health, as determined by medical history, clinical laboratory assessments, vital sign measurements, 12-lead ECG results, and physical examination findings.

Exclusion Criteria:

  1. The subject has a history or clinical manifestations of a significant neurological, cardiovascular, gastrointestinal, pulmonary, hematologic, immunologic, hepatic, genitourinary, endocrine, metabolic, or psychiatric disease that would preclude study participation, as judged by the investigator.
  2. The subject has a positive test result for human immunodeficiency virus Types 1 or 2 antibodies or hepatitis B surface antigen at screening.
  3. The subject has a history of alcoholism or drug abuse within 3 months before screening.
  4. The subject is unable or unwilling to abstain from alcohol, marijuana and related substances, caffeine, cigarette smoking, vaping, or any form of tobacco or nicotine from 48 hours prior to study drug dosing until completing study assessments on Day 5.
  5. The subject is involved in strenuous activity or contact sports within 24 hours of the first dose of study drug or during the study.
  6. The subject has donated blood or blood products >450 mL within 30 days before the first dose of study drug.
  7. The subject has a history of relevant drug and/or food allergies (ie, allergy to setmelanotide or any excipients, or any significant food allergy).
  8. The subject has used prescription drugs from 1 week prior to randomization and throughout the study, except for prescription medications used for the treatment of stable concomitant conditions; examples include the following: diabetes, hypertension, hypercholesterolemia, hyperlipidemia or hypothyroidism. Medications used to treat these indications are allowed, so long as the subject has been on a stable dose for at least 2 weeks prior to randomization and plans to continue a stable dose throughout the study.
  9. The subject has received study drug in another investigational study within 30 days of dosing.
  10. The subject has a positive test result for drugs of abuse (including marijuana, and except positive test results associated with prescription medications that have been reviewed and approved by the investigator) or alcohol at screening or before the first dose of study drug.
  11. The subject has ALT or AST >2 × ULN at screening.
  12. The subject has HbA1c >10%.
  13. The subject has any personal history of cancer (unless stable and in remission for ≥5 years), multiple atypical nevi, nevoid basal cell carcinoma syndrome, or nonmelanoma skin cancer requiring treatment beyond local excision.
  14. The subject has any close family history (parents or siblings) of melanoma.
  15. The subject has significant dermatologic findings relating to melanoma or premelanoma skin lesions, determined as part of a screening comprehensive skin evaluation performed by a qualified dermatologist. Any concerning lesions identified during screening will be biopsied and results known to be benign prior to enrollment. If the pretreatment biopsy results are of concern, the subject may need to be excluded from the study.
  16. The subject has history of clinically significant recent surgery (within 60 days of screening).
  17. The subject has current or recent (within last month) infection or viral illness.
  18. In the opinion of the investigator, the subject is not suitable for entry into the study.

    Additional Exclusion Criteria for Subjects with Renal Impairment Only (Cohorts A, B, and C):

  19. The subject has a positive test result for antibodies to hepatitis C virus with evidence of viral load at screening.
  20. The subject has nephrotic syndrome, defined as urine dipstick 4+ for protein and plasma albumin <3.0 g/dL, and then confirmed if proteinuria >5 g/day.
  21. The subject has renal impairment due to rapidly growing, space-occupying lesions (eg, carcinoma of the kidney, tuberculosis).
  22. Subject has a history of renal transplant.
  23. The subject has a hemoglobin value less than 8.5 g/dL.
  24. The subject has a clinically relevant immunologic disease.

    Additional Exclusion Criteria for Healthy Subjects Only (Cohort D):

  25. The subject has a positive test result for antibodies to hepatitis C virus at screening.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04348175


Contacts
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Contact: Siddhata Pandhare 1 (857)-264-4291 spandhare@rhythmtx.com
Contact: Olga Ohayon oohayon@rhythmtx.com

Locations
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United States, Florida
University of Miami Recruiting
Miami, Florida, United States, 33136
Contact    (305) 243-5930      
Principal Investigator: Richard Preston, MD, MSPH, MBA         
Orlando Clinical Research Center Recruiting
Orlando, Florida, United States, 32809
Contact: Derek Bell    407-240-7876    ddjapic@ocrc.net   
Principal Investigator: Thomas Marbury         
United States, Tennessee
Alliance for Multispecialty Research, LLC Recruiting
Knoxville, Tennessee, United States, 37920
Contact: Nisha Patel    865-305-3784    Nisha.Patel@amrllc.com   
Principal Investigator: William Smith         
United States, Wisconsin
Marshfield Clinic Research Institute Recruiting
Marshfield, Wisconsin, United States, 54449
Contact    800-782-8581 ext 7-5251      
Principal Investigator: Robert Haws         
Sponsors and Collaborators
Rhythm Pharmaceuticals, Inc.
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Responsible Party: Rhythm Pharmaceuticals, Inc.
ClinicalTrials.gov Identifier: NCT04348175    
Other Study ID Numbers: RM-493-029
First Posted: April 16, 2020    Key Record Dates
Last Update Posted: December 31, 2020
Last Verified: December 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Renal Insufficiency
Kidney Diseases
Urologic Diseases