Eye Diseases
Conditions
Brief summary
This is a Phase 1 randomized, double-masked, placebo-controlled study performed with healthy participants to assess the safety and tolerability of laquinimod eye-drops.
Detailed description
Laquinimod administered as an oral capsule formulation has previously been studied in neurodegenerative and autoimmune diseases. The clinical side effect profile of orally administered laquinimod is well-characterized based on this previous experience. This trial will establish a safe and tolerated dose of laquinimod when administered as an eye-drop formulation following single ascending dose (SAD) and multiple ascending dose (MAD) administrations. There are four planned groups in the SAD-part of the study which will enroll 28 participants, if all dose levels are explored. The subsequent MAD-part of the study will enroll another 28 participants.
Interventions
DRUGLaquinimod
Eye-drops
DRUGPlacebo
Eye-drops
Sponsors
Active Biotech AB
Study design
Allocation
RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
MALE
Age
18 Years to 35 Years
Healthy volunteers
Yes
Inclusion criteria
Main inclusion criteria: * In good health according to medical history, physical examination, vital signs, ECG and clinical chemistry, urinary and hematological laboratory tests Main
Exclusion criteria
* Unable or unwilling to use eye-drops * Current usage of contact lenses * History of eye surgery * Sign or symptom of active eye disease * History of an eye disease or other condition that could interfere with eye examinations in the study, or with ocular absorption of the investigational product * History of inflammatory ocular disease * History of cardiovascular or pulmonary disorder * Family history of known or suspected hereditary cardiovascular disease * Autoimmune disease or known family history of autoimmune disease * Any other condition that would contraindicate subject's participation in the clinical study due to safety concerns or compliance with clinical study procedures
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Adverse events | For 7 days post-dose | Type, frequency, seriousness, severity and relationship to treatment |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Investigator-reported eye-toxicities - BCVA | Pre-dose (baseline) and immediately after the intervention | Assessed from change from baseline in Best Corrected Visual Acuity (BCVA) using the Early Treatment Diabetic Retinopathy Study research group (ETDRS) visual acuity chart with objective and subjective refraction. |
| Investigator-reported eye-toxicities - Slit lamp examination | Pre-dose (baseline) and immediately after the intervention | Assessed from change from baseline in slit lamp examination parameters (eyelid swelling, eyelid redness, conjunctival redness, conjunctival chemosis, scleral redness, corneal opacity, iris alterations and anterior chamber flare) graded on a 4-point scale where 0= none, 1= mild, 2= moderate, and 3= severe. |
| Investigator-reported eye-toxicities - Corneal fluorescein staining | At screening visit (baseline) and immediately after the intervention | Assessed from change from baseline in corneal fluorescein staining determined using the NEI/Industry Workshop guidelines. The cornea is divided into five sectors (central, superior, inferior, nasal and temporal) and each sector scored on a 4-point scale, where 0= no staining and 3= maximum staining. |
| Investigator-reported eye-toxicities - Intraocular pressure | At screening visit (baseline) and immediately after the intervention | Assessed from change from baseline in intraocular pressure (mmHg) determined using a Goldmann applanation tonometer. |
| Participant-reported eye-toxicities | Pre-dose (baseline) and immediately after the intervention | Assessed from change from baseline in ocular symptoms score determined using a Visual Analogue Scale with 0-100 range, where 0= no symptom and 100= worst possible discomfort. |
| Peak plasma concentration of laquinimod | Over up to 21 days after (last) dose | Maximal plasma concentration (Cmax) of laquinimod as assessed from samples collected pre-dose and at frequent intervals over 7 days after (last) dose |
| Time to peak plasma concentration of laquinimod | Over up to 21 days) after (last) dose | Time to maximal plasma concentration (tmax) of laquinimod as assessed from samples collected pre-dose and at frequent intervals over 7 days after (last) dose |
| Trough plasma concentration of laquinimod at steady-state | On the last three days of multiple dosing | Minimal plasma concentration (Cmin,ss) of laquinimod as assessed from samples collected pre-dose on Days 12, 13 and 14 within the multiple-dose arm |
| Systemic exposure of laquinimod | Over up to 21 days after (last) dose | Area under the plasma concentration time curve (AUC) of laquinimod |
| Investigator-reported eye-toxicities - Funduscopy in mydriasis | At screening visit (baseline) and immediately after the intervention | Assessed from change from baseline in clinical signs detected by indirect funduscopic inspection of the optic disc, macula, retinal vessels and retinal periphery. |
Countries
Austria
Outcome results
None listed