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A Safety and Tolerability Study of RJX Drug Product in Healthy Participants

14 april 2020 uppdaterad av: Reven Pharmaceuticals, Inc.

A Phase 1, Double-blind, Placebo-controlled, Randomized, Two-Part, Ascending Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Rejuveinix (RJX) in Healthy Participants

Designed as a single center, two-part, double-blind, placebo-controlled, randomized study to assess the safety, tolerability, pharmacokinetics (PK) and pharmacodynamics (PD) of RJX in healthy participants.

Studieöversikt

Status

Avslutad

Detaljerad beskrivning

Part 1 is designed as a Single Ascending Dose (SAD) escalation study with 6 cohorts. Participants will undertake a screening visit between Day -21 and Day -1 to determine eligibility in the study. Those participants that meet the eligibility criteria will be admitted to the study site on the day prior to dosing (Day -1). Participants will receive a single dose of investigational product via IV infusion on Day 1. The first cohort will include the initial dosing of a sentinel group. The remaining participants in Cohort 1 will be dosed if, in the opinion of the investigator or delegate, there are no significant safety concerns identified in the sentinel participants within the first 24 hours after administration of the dose. Participants will be confined to the study site from Day -1 to Day 2 (24 hours post dose) and then required to return to the study site on Day 5 for a final follow up visit. Safety and PK assessments will be performed at selected time points throughout the study.

Part 2 is designed as a Multiple Ascending Dose (MAD) escalation study with 3 cohorts. The MAD arm of the study will commence in parallel with Cohort 6 of Part 1 following completion and review of safety and PK findings for Cohorts 1, 2, 3, 4, and 5 in Part 1. Participants will undertake a screening visit between Day -21 and Day -1 to determine eligibility in the study. Those participants that meet the eligibility criteria will be admitted to the study site on the day prior to dosing (Day -1). Participants will be randomly assigned to receive 1 of 3 proposed doses of investigational product via IV infusion every day for 7 days.Participants will be confined to the study site from Day -1 to Day 8 (24 hours post the final dose on Day 7) and then return to the study site on Day 12 for a final follow up visit. Safety and PK assessments will be performed at selected time points throughout the study.

Studietyp

Interventionell

Inskrivning (Faktisk)

76

Fas

  • Fas 1

Kontakter och platser

Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.

Studieorter

    • Texas
      • San Antonio, Texas, Förenta staterna, 78209
        • ICON Early Phase Services

Deltagandekriterier

Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.

Urvalskriterier

Åldrar som är berättigade till studier

18 år till 70 år (Vuxen, Äldre vuxen)

Tar emot friska volontärer

Nej

Kön som är behöriga för studier

Allt

Beskrivning

Inclusion Criteria:

  1. Healthy male and female participants aged 18 to 50 years inclusive (Cohort 1 to Cohort 5) or 51 to 70 years inclusive (Cohort 6 only),at the time of screening;
  2. Have a body mass index of 18 kg/m2 to 35 kg/m2, inclusive, at screening. In addition, weight cannot exceed 132 kg;
  3. Have negative screening assessment for viral hepatitis (hepatitis B or hepatitis C) and human immunodeficiency virus;
  4. Have negative routine urine drug screen and negative alcohol breath test at screening and Day -1;
  5. A female participant is eligible to participate if she is not pregnant,not breastfeeding, and at least 1 of the following conditions applies:

    1. Not of childbearing potential, defined as surgically sterile (documented hysterectomy, bilateral salpingectomy, tubal ligation or bilateral oophorectomy) or postmenopausal (no menses for 12 months without an alternative medical cause. A high follicle stimulating hormone (FSH) level in the postmenopausal range may be used to confirm a postmenopausal state in women not using hormonal contraception or hormonal replacement therapy; however, in the absence of 12 months of amenorrhea, a single FSH measurement is insufficient);
    2. Of childbearing potential and agrees to use 2 highly effective methods of contraception consistently during the treatment period and for at least 60 days after the last dose of investigational product;
  6. A male participant with a female partner of childbearing potential is eligible to participate if he agrees to use acceptable contraception during the treatment period and for at least 60 days after the last dose of investigational product and refrains from donating sperm during this period;
  7. Clinical laboratory test results within normal reference range for the population or investigator site, or any results that are judged to be not clinically significant by the investigator;
  8. Venous access sufficient to allow for blood sampling per the protocol;
  9. Reliable and willing to make themselves available for the duration of the study and are willing to follow study procedures;
  10. Given written informed consent prior to any study procedures being performed

Exclusion Criteria:

  1. Have a history of clinically relevant cardiovascular disease, cancer, respiratory, hepatic, renal, gastrointestinal, endocrine (diabetes), hematological, or neurological disorders. Cohort 6 only - elderly participants with well controlled hypercholesterolemia on a stable dose of statin therapy or well controlled hypertension on a stable dose of antihypertensive medication(s), excluding diuretics, are allowed in Cohort 6 per the clinical judgment of the investigator.
  2. Have impaired renal function (defined as estimated glomerular filtration rate <90 cc/min/1.73m2 Chronic Kidney Disease Epidemiology Collaboration (CKD-Epi) creatinine equation at screening);
  3. Have a hsCRP above 1.25 × upper limit of normal;
  4. Have a clinically significant abnormality in the 12-lead electrocardiogram (ECG) or prolongation of corrected QT interval by Fredericia (QTcF) >440 ms in males and >450 ms in females;
  5. Have a supine systolic blood pressure (BP) greater than 140 mm Hg or a diastolic BP greater than 90 mm Hg. Up to 2 additional measurements may be undertaken after an appropriate resting interval at screening to confirm eligibility;
  6. Are currently enrolled in a clinical trial involving an investigational product, or are concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study;
  7. Have received an investigational product within the last 3 months;
  8. Have suspected allergies to RJX, related compounds, or any components of the formulation, or history of significant atopy;
  9. Regularly use known drugs of abuse and/or show positive findings on drug screening or Day -1;
  10. Are women who are pregnant, intend to become pregnant, or are lactating;
  11. Participants will be excluded for using any of the following medication:

    • aspirin, multivitamins/vitamins or mineral preparations within 14 days prior to investigational product administration or 24 hours post the last infusion;
    • prescription, herbal or over the counter medications within 14 days of investigational product administration, with the exception of:

      • simple analgesics such as paracetamol, excluding aspirin
      • oral non-steroidal anti-inflammatory drugs
      • thyroid treatment, estrogen replacement therapy
      • hormonal contraception
      • Statins and anti-hypertensives are permitted for elderly participants in Cohort 6 (Part 1) - see inclusion criteria #1
  12. Have donated blood of more than 500 mL within 4 weeks prior to study enrollment;
  13. Have an average weekly alcohol intake that exceeds 21 units per week (males up to age 65) and 14 units per week (males over 65 and females) or are unwilling to stop alcohol consumption for 24 hours prior to study site admission (1 unit = 12 oz or 360 mL of beer; 5 oz or 150 mL of wine; 1.5 oz or 45 mL of distilled spirits). Participants must have a of negative alcohol breath test at Day -1 and no evidence of alcohol abuse in the previous 12 months, defined as > 21 weekly units for males up to age 65 and > 14 weekly units for males over 65 and females;
  14. Have smoked cigarettes in the last 90 days (including occasional smokers who have smoked more than 5 cigarettes per month within the last 90 days);
  15. In the opinion of the investigator or sponsor, are unsuitable for inclusion in the study;
  16. Are investigator site personnel directly affiliated with this study and their immediate families. Immediate family is defined as a spouse, parent, child or sibling, whether biological or legally adopted;
  17. Are Reven employees or employees of third-party organizations involved with the study who require exclusion of their employees.

Studieplan

Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.

Hur är studien utformad?

Designdetaljer

  • Primärt syfte: Grundläggande vetenskap
  • Tilldelning: Randomiserad
  • Interventionsmodell: Parallellt uppdrag
  • Maskning: Dubbel

Vapen och interventioner

Deltagargrupp / Arm
Intervention / Behandling
Experimentell: Part 1; Cohort 1; RJX or Placebo
Participants in Part 1; Cohort 1 will receive a single 0.024 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Experimentell: Part 1; Cohort 2; RJX or Placebo
Participants in Part 1; Cohort 2 will receive a single 0.076 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Experimentell: Part 1; Cohort 3; RJX or Placebo
Participants in Part 1; Cohort 3 will receive a single 0.240 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Experimentell: Part 1; Cohort 4; RJX or Placebo
Participants in Part 1; Cohort 4 will receive a single 0.5 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Experimentell: Part 1; Cohort 5; RJX or Placebo
Participants in Part 1; Cohort 5 will receive a single 0.759 mL/kg dose of RJX or matching placebo on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Experimentell: Part 1; Cohort 6; RJX or Placebo
Participants in Part 1; Cohort 6 will receive a single dose of RJX or matching placebo, to be determined following review of safety and PK data from Cohorts 1 to 5, on Day 1.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Experimentell: Part 2; Cohort 1; RJX or Placebo

Participants in Part 2; Cohort 1 will receive a dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days.

The Part 2; Cohort 1 dose will be 1 log down from the maximum tolerated dose determined in Part 1 or at a dose determined to be safe and well tolerated in Part 1 with an acceptable PK profile.

RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Experimentell: Part 2; Cohort 2; RJX or Placebo
Participants in Part 2; Cohort 2 will receive an escalated dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.
Experimentell: Part 2; Cohort 3; RJX or Placebo
Participants in Part 2; Cohort 3 will receive an escalated dose of RJX or matching placebo, determined based on the findings of Part 1, every day for 7 days.
RJX is an IV infusion formulation. The appropriate RJX dose is calculated based on mL/kg. The administration dose is prepared by adding the appropriate RJX dose to 0.9% sterile saline such that a constant volume of 100 mL per IV infusion is obtained. Infusion time is 100 mL over 45 minutes (+/- 5 minutes).
Matching placebo will be normal saline. To maintain the blind, a sleeve will cover the infusion bag and line such that the appearance will be identical to RJX administration.

Vad mäter studien?

Primära resultatmått

Resultatmått
Åtgärdsbeskrivning
Tidsram
Treatment-related Adverse Events (TEAE) Reporting of RJX
Tidsram: Up to Day 5 for Part 1 and Up to Day 12 for Part 2
Number of participants with indicated AEs receiving RJX as assessed by CTCAE v4 03
Up to Day 5 for Part 1 and Up to Day 12 for Part 2
Safety and Tolerability of RJX as Assessed by Electrocardiograms (ECGs).
Tidsram: Up to Day 2 for Part 1 and Up to Day 8 for Part 2
Number of participants with abnormal and clinically significant findings based on ECG.
Up to Day 2 for Part 1 and Up to Day 8 for Part 2
Safety and Tolerability of RJX as Assessed by Neurological Examinations.
Tidsram: Up to Day 5 for Part 1 and Up to Day 12 for Part 2
Number of participants with clinically significant values and actual changes from baseline of continuous neurological assessments.
Up to Day 5 for Part 1 and Up to Day 12 for Part 2

Samarbetspartners och utredare

Det är här du hittar personer och organisationer som är involverade i denna studie.

Utredare

  • Huvudutredare: Dennis A Ruff, MD, ICON Early Phase Services

Publikationer och användbara länkar

Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.

Studieavstämningsdatum

Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.

Studera stora datum

Studiestart (Faktisk)

24 augusti 2018

Primärt slutförande (Faktisk)

15 januari 2019

Avslutad studie (Faktisk)

15 januari 2019

Studieregistreringsdatum

Först inskickad

29 augusti 2018

Först inskickad som uppfyllde QC-kriterierna

18 september 2018

Första postat (Faktisk)

21 september 2018

Uppdateringar av studier

Senaste uppdatering publicerad (Faktisk)

27 april 2020

Senaste inskickade uppdateringen som uppfyllde QC-kriterierna

14 april 2020

Senast verifierad

1 april 2020

Mer information

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Ytterligare relevanta MeSH-villkor

Andra studie-ID-nummer

  • RPI003

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Ja

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Nej

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