A Study of the Safety and Effectiveness of Orally Administered CR845 in Patients With Osteoarthritis of the Hip or Knee

NCT02524197 | Completed Phase 2

• 1 other identifier: CR845-CLIN2001-PO
• Study Type: interventional
• Target: 81
• Locations: 1 country
• Sites: 5

Brief Summary

To assess the safety and tolerability of orally-administered CR845 in patients with osteoarthritis (OA) of the hip or knee. The study drug is being tested to reduce OA pain, and will be taken twice a day for two weeks, with four different doses (strengths) being tested. From screening period to follow up examination, the study is expected to last for up to 38 days per participant.

Conditions

Osteoarthritis

Keywords

Hip; Knee; Arthritis; pain; CR845; kappa opioid

Outcome Measures

Primary Outcomes (1)

• To assess the Safety and Tolerability of orally-administered CR845 in patients with osteoarthritis of the hip or the knee, in sequentially escalating doses (0.25 mg, 0.50 mg, 1 mg and 5 mg).

  The sentinel group will be dosed and monitored in an inpatient clinic unit for 48 hours, then discharged to complete remainder of treatment at home. Following the evaluation of the first group's safety data, the remaining cohorts will begin enrolling. The safety and tolerability of CR845 will be assessed by physical examination, monitoring of adverse events, vital signs, laboratory evaluations, and fluid balance.

  Sentinel cohort initial 48 hours, all subjects 38 days

Secondary Outcomes (2)

• To characterize the pharmacokinetic (pk) profile of orally-administered CR845 with twice a day (b.i.d) dosing

  48 hours

• To explore the effectiveness of orally administered CR845 in this patient population

  38 days

Study Arms (4)

CR845 0.25 mg

ACTIVE COMPARATOR

Study medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit. Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit. Patients will record their daily intake of study medication on the diary provided.

Drug: CR845 0.25 mg

CR845 0.50 mg

ACTIVE COMPARATOR

Study medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit. Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit. Patients will record their daily intake of study medication on the diary provided.

Drug: CR845 0.50 mg

CR845 1 mg

ACTIVE COMPARATOR

Study medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit. Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit. Patients will record their daily intake of study medication on the diary provided.

Drug: CR845 1 mg

CR845 5 mg

ACTIVE COMPARATOR

Study medication will be taken b.i.d., in the morning (at least 2 hours before breakfast) and later in the afternoon (at least 2 hours before dinner), beginning on the morning of Day1 at the Baseline Visit. Analgesic rescue medication (Acetaminophen) for the treatment of pain will be provided at the Screening Visit. Patients will record their daily intake of study medication on the diary provided.

Drug: CR845 5 mg

Interventions

CR845 0.25 mg DRUG

Subjects will dose orally twice a day with CR845 0.25 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability.

CR845 0.25 mg

CR845 0.50 mg DRUG

Subjects will dose orally twice a day with CR845 0.50 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability.

CR845 0.50 mg

CR845 1 mg DRUG

Subjects will dose orally twice a day with CR845 1 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability.

CR845 1 mg

CR845 5 mg DRUG

Subjects will dose orally twice a day with CR845 5 mg tablets for two weeks. A diary will be kept for recording the individual's pain scores and dosing accountability.

CR845 5 mg

Eligibility Criteria

• Age: 25 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• A patient will be eligible for enrollment if the following criteria are met:
• Voluntarily provides written informed consent to participate in the study prior to any study procedures.
• Is able to speak, read, and communicate clearly in English or Spanish; is able to understand the study procedures.
• Male or female ≥ 25 years of age.
• BMI ≤ 40
• Has OA of the hip or knee according to American College of Rheumatology (ACR) criteria.
• Reports an average pain intensity level ≥ 4 in the index joint at Screening on an NRS.
• Willing to discontinue currently used pain medications beginning 5 days prior to the Baseline Visit and throughout the study.
• If female:
• Of childbearing potential - the patient must be willing to practice an acceptable form of birth control (defined as the use of an intrauterine device; a barrier method with spermicide; condoms, any form of hormonal contraceptives; or abstinence from sexual intercourse) for the duration of treatment and for at least 3 days following the last dose of study drug.
• Of non-childbearing potential - the patient must be surgically or biologically sterile (hysterectomy, bilateral oophorectomy, bilateral tubal ligation, or postmenopausal for at least 1 year).
• Is free of other physical, mental, or medical conditions, which, in the opinion of the Investigator, would make study participation inadvisable.
• Reports average daily pain intensity ≥ 4 in the index joint during the 3 days prior to Baseline on the NRS.

You may not qualify if:

• A patient will be excluded from enrollment if the patient meets any of the following criteria:
• Has had a joint replacement in the index joint.
• Has received an intra-articular injection of corticosteroids or hyaluronic acid in the index joint within 3 months prior to the Screening Visit.
• Has started a new medication for chronic illness within 30 days prior to the Screening Visit.
• Has a history or current diagnosis of substance dependence (except caffeine or nicotine) or alcohol abuse, according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5).
• Has a positive urine drug screen for drugs of abuse at Screening or Baseline.
• Has been diagnosed with a condition of hyperhidrosis or primary hypodipsia.
• Has a history (within 6 months) of clinically meaningful orthostatic changes in vital signs, OR, at Screening, has a decrease in systolic blood pressure by \> 20 mm Hg or a decrease in diastolic blood pressure by 10 mm Hg together with an increase in heart rate of \> 30 beats per minute when transitioning from supine to standing measurements.
• Has a medical condition (e.g., a cardiovascular, pulmonary, hepatic, renal, hematologic, gastrointestinal, endocrine \[adrenal hyperplasia\], immunologic, dermatologic, neurologic, oncologic, or psychiatric condition) or a significant laboratory abnormality that, in the Investigator's opinion, would jeopardize the safety of the patient or is likely to confound the study measurements.
• Has a serum sodium level \> 145 mmol/L at Screening.
• Has impaired renal function indicated by serum creatinine \> 2 × the reference upper limit of normal (ULN).
• Has a serum alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \> 2.5 × the reference ULN, or total bilirubin \> 2 × the ULN at Screening.
• Has, in the opinion of the Investigator, any clinical signs of dehydration or hypovolemia (e.g., symptomatic hypotension) or associated laboratory abnormalities (e.g., elevated hematocrit or elevated blood urea nitrogen \[BUN\] \> 1.5 × the reference ULN) at Screening.
• Has taken opioid or non-opioid pain medication (e.g., nonsteroidal anti-inflammatory drugs \[NSAIDs\] such as naproxen or cyclooxygenase-2 inhibitors) within 5 days prior to study drug administration.
• Has received another investigational drug within 30 days prior to Baseline or has planned to participate in another clinical trial while enrolled in this study.

Sponsors & Collaborators

• Cara Therapeutics, Inc.: lead

Study Sites (5)

Heartland Clinical Research

Omaha, Nebraska, 68134, United States

Location

Matthew Barton, MD

Las Vegas, Nevada, United States

Location

Triad Clinical Trials, LLC

Greensboro, North Carolina, 27410, United States

Location

Altoona Center for Clinical Research

Duncansville, Pennsylvania, 16635, United States

Location

Clinical Investgations of Texas

Plano, Texas, 75075, United States

Location

MeSH Terms

Conditions

Osteoarthritis; Arthritis; Pain

Condition Hierarchy (Ancestors)

Joint Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Paul Tiseo, PhD

  Cara Therapeutics

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2015
• First Posted: August 14, 2015
• Study Start: August 1, 2015
• Primary Completion: January 1, 2016
• Study Completion: January 1, 2016
• Last Updated: January 31, 2017

Record last verified: 2017-01

Locations

US (5)