NCT03776539

A Study to Evaluate the Effects of Renal Impairment on the Pharmacokinetics of ELX-02

Completed Phase 1 Results posted Last updated 13 April 2021

What this trial tests

Phase 1 trial testing ELX-02 in Impaired Renal Function in 24 participants. Completed in 7 August 2019.

Timeline

4 January 2019

Primary endpoint
30 July 2019

7 August 2019

Quick facts

Lead sponsor	Eloxx Pharmaceuticals, Inc.
Phase	Phase 1
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	treatment
Enrollment	24
Start date	4 January 2019
Primary completion	30 July 2019
Estimated completion	7 August 2019
Sites	2 locations across United States

Drugs / interventions tested

• ELX-02 — full drug profile →

Conditions studied

• Impaired Renal Function — all drugs for Impaired Renal Function →

Sponsor

Eloxx Pharmaceuticals, Inc.

Who can join

Adults 18 to 80, any sex, with Impaired Renal Function. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Pharmacokinetic Parameters- Plasma AUC0-24 Primary · 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, and 24 hours after dosing

Area under the curve (AUC0-24) of ELX-02 plasma concentration following a single subcutaneous (SC) dose

Group	Value	95% CI
Mild Renal Impairment	16877.94	± 1714.57
Moderate Renal Impairment	32787.41	± 7410.46
Severe Renal Impairment	64895.29	± 16967.68
Healthy Volunteers	15506.68	± 3444.66

Pharmacokinetic Parameters- Plasma Cmax Primary · 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 168 (Day 8) hours after dosing

Peak Plasma Concentration (Cmax) of ELX-02 following a single subcutaneous (SC) dose in subjects with normal renal function, mild, moderate, or severe renal impairment

Group	Value	95% CI
Mild Renal Impairment	2993.33	± 280.33
Moderate Renal Impairment	3688.33	± 525.56
Severe Renal Impairment	4273.33	± 947.49
Healthy Volunteers	2995.00	± 568.99

AUC0-inf Primary · 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, 24, 36, 48, 72, and 168 (Day 8) hours after dosing

Area under the curve (AUC0-inf) of ELX-02 plasma concentration following a single subcutaneous (SC) dose

Group	Value	95% CI
Mild Renal Impairment	16997.41	± 1776.84
Moderate Renal Impairment	35179.57	± 9198.37
Severe Renal Impairment	110925.53	± 49098.37
Healthy Volunteers	15214.30	± 2913.01

Pharmacokinetic Parameters - Plasma Tmax Primary · 0.25, 0.5, 0.75, 1, 2, 4, 6, 12, and 24 hours after dosing.

Time to maximum concentration (Tmax) of ELX-02 plasma concentration following a single subcutaneous (SC) dose

Group	Value	95% CI
Mild Renal Impairment	1.00	0.75 – 2.00
Moderate Renal Impairment	1.00	0.75 – 2.00
Severe Renal Impairment	2.00	1.00 – 6.00
Healthy Volunteers	1.50	0.73 – 2.00

Urine Pharmacokinetics Parameter - Ae0-t Primary · Pre-dose (first void in the morning of Day 1), 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36, 36-48, and 48-72 hours post-dose

Cumulative amount of unchanged drug excreted into urine (Ae0-t) of ELX-02 following a single subcutaneous (SC) dose

Group	Value	95% CI
Mild Renal Impairment	61.50	± 19.37
Moderate Renal Impairment	72.10	± 26.45
Severe Renal Impairment	54.86	± 8.74
Healthy Volunteers	69.22	± 17.70

Urine Pharmacokinetic Parameter - Rmax Primary · Pre-dose (first void in the morning of Day 1), 0-3, 3-6, 6-9, 9-12, 12-18, 18-24, 24-36, 36-48, and 48-72 hours post-dose

Maximum rate of urinary extraction (Rmax) of ELX-02 following a single subcutaneous (SC) dose

Group	Value	95% CI
Mild Renal Impairment	9.18	± 2.91
Moderate Renal Impairment	8.06	± 5.91
Severe Renal Impairment	3.11	± 1.81
Healthy Volunteers	12.09	± 2.82

Number of Patients Reporting Treatment-Emergent Adverse Events (TEAEs) [Safety] Primary · 1-8 days

TEAEs are undesirable events not present prior to medical treatment, or an already present event that worsens either in intensity or frequency following the study treatment

Group	Value	95% CI
Mild Renal Impairment	0
Moderate Renal Impairment	0
Severe Renal Impairment	2
Healthy Volunteers	9

Adverse events — posted to ClinicalTrials.gov

Time frame: From the date of the signing of the consent form until follow-up visit on Day 8.. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Group 1

Serious: 0/6 (0%)

Deaths: 0/6

Group 2

Serious: 0/6 (0%)

Deaths: 0/6

Group 3

Serious: 0/6 (0%)

Deaths: 0/6

Group 4

Serious: 0/6 (0%)

Deaths: 0/6

Other adverse events (6 terms — click to expand)

Reaction	System	Group 1	Group 2	Group 3	Group 4
Injection site erythema	General disorders	—	—	—	—
Injection site pruritus	General disorders	—	—	—	—
Injection site induration	General disorders	—	—	—	—
Blood pressure decrease	Investigations	—	—	—	—
Dizziness	Nervous system disorders	—	—	—	—
Back pain	Musculoskeletal and connective tissue disorders	—	—	—	—

Data from ClinicalTrials.gov NCT03776539 adverse events section.

Sponsor's own description

Phase 1 - Pharmacokinetics in Patients with Impaired Renal Function

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Mutation-Directed Therapeutics for Neurofibromatosis Type I.
   Leier A, Bedwell DM, Chen AT, Dickson G, et al · · 2020 · cited 23× · PMID 32408052 · DOI 10.1016/j.omtn.2020.04.012
2. Pharmaceuticals Promoting Premature Termination Codon Readthrough: Progress in Development.
   Li S, Li J, Shi W, Nie Z, et al · · 2023 · cited 21× · PMID 37371567 · DOI 10.3390/biom13060988
3. Phase 1 Renal Impairment Trial Results Supports Targeted Individualized Dosing of ELX-02 in Patients With Nephropathic Cystinosis.
   Haverty T, Wyatt DJ, Porter KM, Leubitz A, et al · · 2021 · cited 5× · PMID 33355924 · DOI 10.1002/jcph.1807