A Clinical Study to Measure the Effect of OP-101 After Being Administered Subcutaneous in Healthy Volunteers

• ClinicalTrials.gov Identifier: NCT04321980
• Recruitment Status: Completed
• First Posted: March 26, 2020
• Results First Posted: June 14, 2021
• Last Update Posted: June 14, 2021
• Sponsor: Orpheris, Inc.
• Information provided by (Responsible Party): Orpheris, Inc.

Study Description

Brief Summary:

A clinical study to measure the Safety, Tolerability, and Pharmacokinetics of OP-101 After Subcutaneous Administration in Healthy Volunteers

Condition or disease	Intervention/treatment	Phase
Healthy	Drug: OP-101	Phase 1

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 8 participants
• Allocation: Non-Randomized
• Intervention Model: Sequential Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 1 Open-Label Single-Ascending Dose Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of OP-101 (Dendrimer N-acetyl-cysteine) After Subcutaneous Administration in Healthy Volunteers
• Actual Study Start Date: March 19, 2020
• Actual Primary Completion Date: May 22, 2020
• Actual Study Completion Date: May 22, 2020

Arms and Interventions

Arm	Intervention/treatment
Experimental: Cohort 1; Subjects in Cohort 1 will be administered 4 mg/kg OP-101 as a subcutaneous (SC) injection.	Drug: OP-101; Subcutaneous injection of OP-101 in healthy volunteers
Experimental: Cohort 2; Subjects in Cohort 2 will be administered 8 mg/kg OP-101 as a SC injection.	Drug: OP-101; Subcutaneous injection of OP-101 in healthy volunteers

Outcome Measures

Primary Outcome Measures :

1. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events [ Time Frame: Up to Day 15 ]
   An adverse event (AE) was defined as any untoward medical occurrence in a clinical investigation participant administered a pharmaceutical product, which does not necessarily have a causal relationship with this treatment. A TEAE (treatment-emergent adverse event) was defined as an AE that emerges, having been absent prior to the study, or an AE that worsens in severity after the first dose of the study drug. Serious AE (SAE) was an AE resulting in any of the following outcomes: death; life-threatening adverse event, required hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect, or a medically important event.

Secondary Outcome Measures :

1. Pharmacokinetics: Maximum Observed Plasma Concentration (Cmax) of OP-101 [ Time Frame: Pre-dose, 0.5 hours and 1, 2, 4, 6, 8, 10, 12, 16, 24, 30-36, 48 hours post-dose ]
   Cmax: maximum observed plasma concentration.
2. Pharmacokinetics: Time to Reach Maximum Plasma Concentration (Tmax) of OP-101 [ Time Frame: Pre-dose, 0.5 hours and at 1, 2, 4, 6, 8, 10, 12, 16, 24, 30-36, 48 hours post-dose ]
   Tmax: time to reach maximum observed plasma concentration.
3. Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to the Last Quantifiable Concentration (AUC0-last) of OP-101 [ Time Frame: Pre-dose, 0.5 hours and 1, 2, 4, 6, 8, 10, 12, 16, 24, 30-36, 48 hours post-dose ]
   AUC0-last: Area under the concentration versus time curve from time zero to the last quantifiable concentration (Clast).
4. Pharmacokinetics: Area Under the Concentration Versus Time Curve From Time Zero to 48 Hour Post Dose Time Point (AUC0-48) of OP-101 [ Time Frame: Pre-dose, 0.5 hours and 1, 2, 4, 6, 8, 10, 12, 16, 24, 30-36, 48 hours post-dose ]
   Area under the concentration versus time curve from time zero to 48 hour post dose time point.
5. Pharmacokinetics: Renal Clearance (CLR) for OP-101 [ Time Frame: Pre-dose, 0 to 4, 4 to 8, 8 to 12, 12 to 18, 18 to 24, and 24 to 48 hours post dose ]
   CLR was defined as renal clearance of the drug from plasma utilizing the AUC and cumulative amount of unchanged study drug excreted into the urine (Ae) to the same duration (as Amount recovered/AUC at 0-48 hours).

Eligibility Criteria

• Ages Eligible for Study: 18 Years to 65 Years (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

Criteria

Inclusion Criteria:

• Is a healthy man or woman age 18 to 65 years, inclusive, at the Screening Visit;
• Has the ability to understand and sign the written Informed Consent Form (ICF) and local medical privacy authorization forms, which must be obtained prior to any study related procedures being completed;
• Body mass index (BMI) between 18 and 32 kg/m2, inclusive;
• Is in general good health, based upon the results of a medical history assessment, physical examination, vital signs, and laboratory profile, as judged by the Investigator;
• Female subjects of non-childbearing potential must be either surgically sterile (hysterectomy, bilateral tubal ligation, salpingectomy, and/or bilateral oophorectomy at least 26 weeks before the Screening Visit) or postmenopausal, defined as spontaneous amenorrhea for at least 2 years, with follicle-stimulating hormone (FSH) in the postmenopausal range at screening, based on the central laboratory's ranges;
• Female subjects of childbearing potential (ie, ovulating, premenopausal, and not surgically sterile) and all male subjects must use a medically accepted contraceptive regimen (including hormonal contraceptives) during their participation in the study and for 30 days after the last administration of study drug. Medically accepted contraceptive methods are defined as those with 90% or greater efficacy;

• Acceptable methods of contraception for male subjects enrolled in the study include the following:

  • Condoms or surgical sterilization of subject at least 26 weeks before the Screening Visit (vasectomy);

• Acceptable methods of contraception for female subjects enrolled in the study include the following:

  • Surgical sterilization of subject at least 26 weeks before the Screening Visit (includes hysterectomy or bilateral tubal ligation, oophorectomy, or salpingectomy);
  • Intrauterine device for at least 12 weeks before the Screening Visit;
  • Hormonal contraception (oral, implant, injection, ring, or patch) for at least 12 weeks before the Screening Visit; or
  • Diaphragm;
• If male, subjects must agree to abstain from sperm donation through 90 days after administration of the last dose of study drug;
• Female subjects may not be pregnant, lactating, or breastfeeding;
• Female subjects of childbearing potential must have negative result for pregnancy test at screening and Check-in;
• Subjects must have a negative test result for hepatitis B surface antigen (HBsAg), hepatitis C virus antibody (HCVab), and human immunodeficiency virus (HIV) antibody at screening;
• Subjects must have an estimated glomerular filtration rate (eGFR) of ≥90 mL/min/1.73m2 at screening;
• Subjects must have a negative urine test for drugs of abuse (opiates, benzodiazepines, amphetamines, cannabinoids, cocaine, barbiturates, and phencyclidine), cotinine, and breath alcohol test at screening and Check-in; and
• Subjects must be willing and able to abide by all study requirements and restrictions.

Exclusion Criteria:

• Evidence of clinically significant hematologic, renal, endocrine, pulmonary, cardiac, gastrointestinal (GI), hepatic, psychiatric, neurologic, immunologic, allergic disease (including multiple or clinically significant drug allergies), or any other condition that, in the opinion of the Investigator, might significantly interfere with the absorption, distribution, metabolism, or excretion of study drug, or place the subject at an unacceptable risk as a participant in this study;
• History of malignancy (other than successfully treated basal cell or squamous cell skin cancer);
• History or presence of an abnormal ECG that, in the opinion of the Investigator, is clinically significant;
• Laboratory results (serum chemistry, hematology, coagulation, and urinalysis) outside the normal range at screening and Check-in and considered clinically significant in the opinion of the Investigator. Any elevation of aspartate transaminase (AST) and alanine transaminase (ALT) above the upper limit of normal at screening and/or Check-in is exclusionary. One retest of an exclusionary laboratory result is allowed at the discretion of the Investigator;
• Has had an acute illness considered clinically significant by the Investigator within 30 days prior to screening;
• History of alcoholism or drug abuse within 2 years prior to screening;
• Has used any product containing nicotine within 90 days prior to screening or intends to use any product containing nicotine during the course of the study;
• Has had any immunizations (live vaccines) in the 4 weeks prior to screening;
• Has used medications that affect GI motility or gastric emptying; such as metoclopramide, proton pump inhibitors, and H2 blockers; within 30 days prior to Day 1;
• Has used any prescription or over-the-counter medication (with exception of acetaminophen), vitamins/herbal supplements (with the exception of hormonal contraceptives) within 14 days prior to Day 1;
• Has used any other study drug within 30 days or 5 half-lives of the drug (whichever is longer) prior to Day 1;
• Has lost or donated >450 mL of whole blood or blood products within 30 days prior to screening;
• Investigator has reason to believe that the subject may be unable to fulfill the protocol visit schedule or requirements;
• Has any finding that, in the view of the Investigator or Medical Monitor, would compromise the subject's safety requirements; or
• Is employed by the Sponsor, the Contract Research Organization (CRO), or the study site (permanent, temporary contract worker, or designee responsible for the conduct of the study), or is a family member (spouse, parent, sibling, or child) of the Sponsor, CRO, or study site employee.

Contacts and Locations

Locations

Australia, South Australia

CMAX

Adelaide, South Australia, Australia, 5000

Sponsors and Collaborators

Orpheris, Inc.

  Study Documents (Full-Text)

Documents provided by Orpheris, Inc.:

Study Protocol  [PDF] March 17, 2020

Statistical Analysis Plan  [PDF] May 28, 2020

More Information

• Responsible Party: Orpheris, Inc.
• ClinicalTrials.gov Identifier: NCT04321980
• Other Study ID Numbers: OP-101-003
• First Posted: March 26, 2020
• Results First Posted: June 14, 2021
• Last Update Posted: June 14, 2021
• Last Verified: May 2021

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: Yes