Medical condition: Osteoarthritis Medical condition in lay language: In osteoarthritis, the protective cartilage on the ends of the bones breaks down, causing pain, swelling and problems moving the joint. Bony growths develop, and area can become swollen and red Therapeutic areas: Diseases [C] - Musculoskeletal Diseases [C05] Musculoskeletal Diseases
Conditions
Interventions
For Healthy volunteers (Part 1), multiple-dose administration of Mavatrep or placebo will occur for 21 consecutive days. A loading dose is planned to be administered BID on Day 1 and Day 2, followed b
patients randomised to receive placebo will receive placebo BID on Day 1 and Day 2.
Sponsors
MAC Clinical Research
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Participant is aged between 18 and 55 years old, inclusive (Part 1 only). 2. Participant is aged between 25 and 79 years old, inclusive (Part 2 only). 3. Participant has a body mass index (BMI) of =32 kg/m2 (Part 1) or =40 kg/m2 (Part 2). 4. Participant must answer all 10 questions to ensure their understanding of the Burn Prevention Measures correctly at Screening. If participants do not answer all 10 questions correctly the first time, they will be permitted to ask questions of the Investigator or study staff and take the quiz a second time. 5. Healthy and free from clinically significant illness or disease as determined by medical history, physical examination, clinical laboratory evaluations, vital signs, 12-lead ECG and other tests performed at Screening and/or Day -1 (Part 1 only). In case of uncertain or questionable results, tests performed during Screening and/or Day 1 may be repeated to confirm eligibility or judged to be clinically irrelevant for healthy participants. Patients in Part 2 must also meet the following additional criteria before they can be randomised for treatment: 6. Patient has moderate to severe unilateral or bilateral knee OA pain (can include post-traumatic OA from historic injuries, at Investigator discretion); must be able to identify one knee as the target knee for pain assessments during the study as confirmed by: 6.1. Clinical diagnosis of OA of the knee based on criteria defined by the American College of Rheumatology. If a patient does not have radiographic evidence of OA of the target knee joint (either X-ray, computerised tomography [CT] or magnetic resonance imaging [MRI] scan) documented in their medical history within 48 months prior to Screening, they must have weight-bearing anterior-posterior tibiofemoral and lateral X-rays as part of the Screening process. If a patient has no prior diagnosis of OA but fulfils the criteria for the American College of Rheumatology for OA, they can be included in the study at the discretion of the Investigator and after confirmation of OA with radiographic evidence as part of Screening assessments. 6.2. Patients must be able to designate one target knee for the purpose of pain assessments during the study (the pain in the knee target joint should exceed the pain experienced in other joints [including the contralateral knee joint and/or ipsilateral hip joint] and pain experienced from any concomitant condition). 7. Baseline score of =4 to =9 on an 11-point NRS (‘on a scale of 0 to 10, where 0 = no pain and 10 = worst imaginable pain, how would you rate your level of pain in the past 24 hours?’) calculated as the average pain intensity during the last 7 days prior to randomisation (patients need to have a minimum of 5 out of 7 possible assessments [QD assessments, 24-hour average NRS]). 8. Medically stable based on physical examination, medical history, vital signs, 12 lead ECG and clinical laboratory tests including thyroid stimulating hormone (TSH) performed at Screening and Day -1. If there are abnormalities, they must be consistent with the underlying illness in the study population. If the results of the serum chemistry panel (including liver enzymes), haematology, or urinalysis are outside the normal reference ranges, the patient may be included only if the Investigator judges the abnormalities or deviations from normal to be not clinically significant or to be appropriate and reasonable for the population under study. This determination must be record
Exclusion criteria
Exclusion criteria: 1. Have occupations or hobbies in which they are at high risk of sustaining thermal burns. 2. Previous enrolment and dosing in this or other trials with Mavatrep. 3. Received prior treatment with any other TRPV1 antagonist or agonist. 4. History of, or current evidence of prolonged QTcF interval >450 msec for male participants or >470 msec for female participants, or a QTcF interval <350 msec, at Screening or Day -1, or a family history of long or short QT syndrome or Torsades de Pointes. 5. Significant renal dysfunction, defined as creatinine clearance calculated using the Cockcroft-Gault equation <60 mL/min (Part 1) or <45 mL/min (Part 2). 6. Significant suicide risk as defined in the protocol. 7. History of malignancy within the past 5 years prior to Screening except for appropriately treated: cutaneous basal cell or squamous cell cancers; cured cervical cancer/cervical cancer in-situ; and (Part 2 only) low-grade stable prostate cancer. 8. Known allergies, hypersensitivity, or intolerance to Mavatrep or its excipients. 9. Any new or unresolved neurologic deficits, including progressive deficits, within 6 months before Screening. Transient neurologic deficits that are resolved within this period can be allowed if approved by the Investigator. 10. History of epilepsy or other seizure disorder. 11. Medical history of significant liver insufficiency; chronic hepatitis B or C, or human immunodeficiency virus (HIV), presence of active hepatitis B or C within the past 3 months. 12. Clinically relevant history of hypersensitivity, allergy, or contraindication to paracetamol/acetaminophen (or ingredients). 13. The participant received botulinum toxin or any other neurotoxin injections within 6 months prior to dosing. 14. Active peripheral neuropathy, paraesthesia or dysesthesia, or any other previously diagnosed neurologic condition causing paraesthesia and dysaesthesia. Patients in Part 2 who meet any of the following additional criteria will be excluded from study participation: 15. Has any other chronic pain condition that, in the Investigator’s opinion, would interfere with the patient’s ability to assess their OA pain. 16. Any patient with radiographic evidence of another disease which may be contributing to their knee pain (including but not limited to osteonecrosis, severe malalignment, benign or malignant bony lesions) will be excluded. 17. Intra-articular injections into the target knee of either corticosteroid (within 3 months of dosing) or hyaluronan (within 1 month of dosing). Intra-articular injections of corticosteroid into any other joint within 1 month of dosing. 18. Use of topical capsaicin (e.g., creams, patches) within 1 week of dosing, or intra-articular use of capsaicin within 1 month of dosing. 19. History and clinical signs at the target knee joint of any other type of arthropathy (including but not limited to rheumatoid arthritis, psoriatic arthritis, septic arthritis, gout, pseudogout, metabolic and autoimmune arthropathies). 20. Severe depression as defined by a score of =29 on the Beck Depression Inventory®–II (BDI-II) at Screening.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| The primary endpoints of the study are the following Mavatrep PK parameters, calculated on Day 1, Day 14 and Day 21 where possible: 1.Cmax 2.tmax 3.AUC24 4.Minimum plasma drug concentration (Cmin) 5.Apparent clearance at steady state (CLSS/F) 6.Apparent volume of distribution at steady state (VdSS/F) 7.Mean residence time (MRT) 8.Accumulation ratio based on Cmax and AUC24 9.AUC0-8 (Day 21 only) 10.t1/2 Pharmacokinetic blood samples will be also collected throughout a 3-week follow-up period to fully characterise the elimination phase of the PK profile and calculate t1/2. | — |
Secondary
| Measure | Time frame |
|---|---|
| The secondary endpoint of the study is the comparison of safety data between Mavatrep versus placebo as assessed by AE reporting, physical examinations, vital signs (heart rate and blood pressure), tympanic temperature, 12-lead ECG and clinical laboratory assessments on Day -1, Day 1 through to Day 42 (ET) | — |
Countries
United Kingdom
Contacts
Public ContactShoona Vincent
Outcome results
None listed