Acute Gouty Arthritis, Acute Pain, Gout Flare
Conditions
Keywords
ketorolac, topical, intravenous
Brief summary
This study will be a phase 1, open-label, bioavailability, safety and PK study of topically applied transcutaneous ketorolac tromethamine gel 12.5% (/w) (NOV-1776) versus intravenous administration of approved ketorolac tromethamine injection, USP (15mg/mL) comparator in healthy volunteers, including an evaluation of safety, tolerability, and efficacy in gout participants with flare-up.
Detailed description
Participants will be in the age range of 18 - 64 years of age (Cohort 1) and 18 - 70 years of age (Cohorts 2 and 3). This study will be conducted in three consecutive cohorts (see Figure 1). Cohorts 1 and 2 is conducted inpatient, while Cohort 3 is conducted outpatient. \- Cohort 1: Open-label, single-day, multiple-dose (three doses), in approximately 8 adult healthy volunteers. Study participants will be admitted to the clinic and receive one intravenous dose of ketorolac tromethamine injection, USP over the course of one day for one treatment period, and three doses of topical drug product over the course of 1 day, 6 hours apart for each of 3 subsequent treatment periods of this Cohort 1. The next dose begins after a 2-day wash-out period, and there are three dose levels for the topically applied transcutaneous ketorolac tromethamine gel 12.5% (w/w) (NOV-1776) to be compared to one intravenous administration of 2 ml of ketorolac tromethamine injection, USP (5 mg/mL). Safety Review Committee meeting to review Cohort 1 data and approve continuance to Cohort 2. * Cohort 2: Open-label, 1-arm, 5-day, multiple-dose PK, safety in approximately 12 adult healthy volunteers at the maximum tolerated dose demonstrated by Cohort 1. Study participants will be admitted to the clinic and receive three doses of drug product, 6 hours apart, over the course of 5 days. Cohort 1 participants are eligible to participate in Cohort 2. Safety Review Committee meeting to review Cohort 1 and 2 data and approve continuance to Cohort 3. * Cohort 3 will be an open-label, 1-arm, 5-day, multiple-dose safety, toleration, and efficacy design in 10 adult gout participants with flare-up
Interventions
DRUGKetorolac Tromethamine 15 MG/ML
Single intravenous administration of Ketorolac Tromethamine injection in Cohort 1 on day 1
DRUGKetorolac Tromethamine
Three doses of topical ketorolac tromethamine over the course of 1 day, 6 hours apart for each of 3 subsequent treatment periods in cohort 1 Three doses of Ketorolac Tromethamine, 6 hours apart, over the course of 5 days in cohorts 2 and 3
Sponsors
Novilla Pharmaceuticals
Study design
Allocation
NA
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
All cohost 1 subjects receive single ketorolac tromethamine injection, followed by escalating doses of ketorolac tromethamine gel Cohort 2 and 3 subjects receive doses of ketorolac tromethamine gel for 5 days
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
Inclusion criteria
Cohorts 1 and 2 * Evidence of a personally signed and dated informed consent form (ICF) in English * Healthy study participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures, * Body mass index (BMI) from 18.0 to 32.0 kg/m2, inclusive; and body weight of at least 50 kg (110 lbs) and Resting supine systolic blood pressure from 90 to 140 mmHg and supine diastolic blood pressure from 40 to 90 mmHg * Male participants must agree to utilize a barrier contraceptive method for the duration of the study and agree to avoid sperm donation for at least 90 days after completing study participation and female participants must be of non-childbearing potential (defined as either surgically sterile or at least 1 year post-menopausal; post- menopausal is defined as no menses for 12 months and confirmed by FSH level ≥ 40 mIU/mL); or must be using a highly effective method of contraception Cohort 3 - additional requirements \- Medical diagnosis of gout for at least 2 years and1 - 2 acute gout flare-ups within the last 12 months
Exclusion criteria
Cohorts 1. 2 and 3 * Presence or history of any disorder that may prevent the successful completion of Cohort 1 \[or Cohort 2, as appropriate\] * Allergy or sensitivity to non-steroidal anti-inflammatory drugs (NSAIDs), ketorolac tromethamine, or any components of the formulation and /or history of significant allergies and hypersensitivity reactions (hives, breathing difficulty, etc.) to aspirin or any other medications, either prescription or nonprescription, including dietary supplements or herbal medications. * A clinically significant history of or current abnormality or disease of any organ system, including renal, hepatic, gastrointestinal (e.g., bleeding, ulcers, perforation), cardiovascular (e.g., cardiovascular thrombotic events, myocardial infarction, stroke) pulmonary (including chronic asthma), endocrine (e.g., diabetes), central nervous system, hematologic system (e.g., bleeding disorders), psychiatric disease, seizure, epilepsy, severe head injury, multiple sclerosis, or other known neurological conditions, or recent surgery that the Investigator deems clinically significant. * History or recent occurrence of clinically significant skin disorders (including photosensitivity reactions, eczema, and psoriasis) or any surgical or medical condition or skin modification at the site of drug application that may interfere with the absorption, distribution, metabolism or excretion of the test article. * Hemoglobin \< 13.2 g/dL or \< 132 g/L (males) and \< 11.7 g/dL or \< 117 g/L (females); Hematocrit \< 38.5% (males) and \< 35% (females) platelet count \< 100,000 platelets per microliter (males and females); at Screening * Uncontrolled hypertension with consistent blood pressure higher than 140 / 90 mmHg. * within 7 days prior to study enrollment, acute illness (e.g., nausea, vomiting, fever, or diarrhea), use of any prescription OTC or dietary or herbal supplements, including ketorolac tromethamine * within 60 days prior to study enrollment, plasma or blood donation * within 90 days prior to study enrollment, use of hepatic or renal clearance altering agents (e.g., erythromycin, cimetidine, barbiturates, phenothiazines, St. John's Wort, etc.) * Positive finding on urine drug screen ( (amphetamines, barbiturates, benzodiazepines, cannabinoids, cocaine, cotinine, methadone, and opiates or other substances deemed inappropriate); Positive serological findings for any of the following: Human Immunodeficiency Virus (HIV), Hepatitis B surface antigen, Hepatitis C antibody, or Hepatitis A IgM tests at Screening. * Female participants who are pregnant or breastfeeding.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Related Adverse Events as Assessed by CTCAE v5.0 | 15 days | Assessment of adverse events |
| Area Under the Plasma Concentration Versus Time Curve (AUC) of topical ketorolac tromethamine | 15 days | Assessment of bioavailability of topical ketorolac tromethamine |
Countries
Australia
Contacts
Primary ContactNovotech CRO
Outcome results
None listed