Cystinosis
Conditions
Keywords
Nephropathic Cystinosis, Cysteamine, Delayed-Release Cysteamine, Orphan Disease, CTNS Protein, Human
Brief summary
The purpose of this study is to gather information about the effectiveness (how well it works to treat cystinosis) and safety of a new form of cysteamine bitartrate called RP103, compared to the already-approved drug cystinosis patients are taking called Cystagon®. In cystinosis, the body builds up cystine. When taken regularly, the active ingredient of Cystagon® (cysteamine bitartrate) reduces cystine in the body. RP103 has the same active ingredient as Cystagon® and is designed to reduce cystine in a similar way that Cystagon® does. To decide if RP103 is better than Cystagon®, the study will look at two types of blood tests. One test is pharmacodynamics (PD), which measures the amount of white blood cell (WBC) cystine after taking study drug. WBC cystine is a laboratory test used to find out if cysteamine bitartrate is reducing cystine levels in the body. The second test is pharmacokinetics (PK), which measures the amount of cysteamine in the blood after taking the drug. RP103 is different from Cystagon®: Instead of the cysteamine bitartrate being absorbed from the stomach, RP103 is designed to be absorbed from the small intestine. This may make the effects of the drug last longer, so that it can be taken twice a day instead of four times a day like Cystagon®. Some cystinosis patients have bad breath (halitosis) when they take Cystagon®. Study participants who experience bad breath with Cystagon® will be asked if they would like to participate in an optional halitosis substudy to investigate this issue by collecting some extra PK blood samples.
Detailed description
Study with completed results acquired from Horizon in 2024.
Sponsors
Amgen
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Male or female with a documented diagnosis of cystinosis * On a stable dose of Cystagon® at least 21 days prior to Screening * WBC cystine level \> 1 nmol 1/2 cystine/mg of protein, on average over at least 2 measurements collected during the 2 years prior to Screening * No clinically significant change in liver function tests, i.e. 1.5 times upper limit of normal (ULN) for alanine aminotransferase and aspartate aminotransferase, and/or 1.5 times ULN for total bilirubin, within 6 months prior to Screening * No clinically significant change in renal function, i.e. estimated glomerular filtration rate (GFR) within 6 months prior to Screening * Must have an estimated GFR \> 20 mL/minute/1.73m\^2 (using the equation from Schwartz 2009 J Am Soc Nephrol 20:629-647) * Female subjects who are sexually active and of childbearing potential, i.e. not surgically sterile (tubal ligation, bilateral oophorectomy, or hysterectomy) or at least 2 years naturally postmenopausal must agree to use an acceptable form of contraception from Screening through completion of the study. Acceptable forms of contraception for this study include hormonal contraceptives (oral, implant, transdermal patch, or injection) at a stable dose for at least 3 months prior to Screening, barrier (spermicidal condom or diaphragm with spermicide), intrauterine device, or a partner who has been vasectomized for at least 6 months. * Subject or their parent or guardian must provide written informed consent, assent (where applicable), prior to participation in the study
Exclusion criteria
* Younger than 12 years of age * Current history of the following conditions or any other health issues that make it, in the opinion of the investigator, unsafe for study participation: * Inflammatory bowel disease, if currently active, or prior resection of the small intestine; * Heart disease (e.g., myocardial infarction, heart failure, unstable arrhythmias, or poorly controlled hypertension) within 90 days prior to Screening; * Active bleeding disorder within 90 days prior to Screening; * History of malignant disease within 2 years prior to Screening * Hemoglobin level of \< 9 g/dL at Screening or, in the opinion of the investigator, a hemoglobin level that would make it unsafe for study participation * Known hypersensitivity to cysteamine and penicillamine * Female subjects who are nursing, planning a pregnancy, or are known or suspected to be pregnant * Subjects who, in the opinion of the investigator, are not able or willing to comply with study requirements.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Average Difference Between Morning and Non-Morning Log White Blood Cell (WBC) Cystine Values | While taking Cystagon® (Months 1, 2, 3): within 15 minutes pre-morning (AM) and pre-non AM dose. During 3 months of RP103 (Months 5, 6, 7): 30 minutes post-AM and post-evening (PM) dose. | The primary analysis of WBC cystine was performed using the natural log transformed WBC cystine level; the log transformation is a normalizing transformation. For each participant, the difference between the morning and corresponding non-morning log WBC cystine value (non-morning minus morning) at each monthly visit during the Cystagon® phase (Months 1, 2, and 3) was computed and these differences were averaged. The average difference between morning and non-morning log WBC cystine value was similarly computed for each participant during the RP103 phase (Months 5, 6, and 7). The primary analysis compared within-subject pairs (Cystagon® phase paired with RP103 phase) of non-morning minus morning average differences of log WBC cystine level. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | From first dose of study drug to 7 days after last dose. Median duration of exposure was 91 days (range 82-108) for Cystagon® phase, 119 days (range 98-137) for the RP103 phase, and 861 days (range 30 - 1350) during the long-term RP-103 phase. | AE: any untoward medical occurrence that does not necessarily have a causal relationship with study drug. SAE: any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or is medically significant, and though not included in the above list, is an important medical event, according to the Investigator. Treatment-emergent adverse events (TEAEs) occurred after first dose of study drug. Clinically significant abnormalities in laboratory values (hematology, blood chemistry, urinalysis), electrocardiograms (ECGs), vital signs, and physical examinations were to be reported as adverse events and so are included in this summary of TEAEs |
| Halitosis Substudy: Maximum Plasma Concentration (Cmax) for Plasma Cysteamine | While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose | Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of dimethylsulfide (DMS) in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state pharmacokinetic (PK) samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered. |
| Halitosis Substudy: Time to Cmax (Tmax) for Plasma Cysteamine | While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose | Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered. |
| Area Under the Plasma Concentration Time Curve From Time Point 0 Through the Last Measurable Point (AUC0-t) for Plasma Cysteamine | While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose | Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered. |
| Halitosis Substudy: Expired Air DMS Concentrations | While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose 30 min post-dose, 2, 3, 4 and 6 hours post-dose. While taking RP103 (Month 4, 5, or 7): Within 15 min. prior to morning dose. 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose | Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered. |
Countries
Belgium, France, Italy, Netherlands, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| All Participants Cystagon® Phase: From Screening and during Months 1, 2, 3 participants received their usual dose of Cystagon® Q6H.
RP103 Phase: During Months 3.5, 4, 5, 6, 7 participants received RP103 Q12H.
Long Term Phase: On or after Month 7, for the remainder of study participants received RP103 Q12H. | 41 |
| Total | 41 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Long Term Extension Phase | Adverse Event | 1 |
| Long Term Extension Phase | Consent Withdrawn by Subject | 2 |
| Long Term Extension Phase | Sponsor Decision | 2 |
| RP103 Phase | Non-compliance | 1 |
Baseline characteristics
| Characteristic | All Participants |
|---|---|
| Age, Continuous | 24.5 years STANDARD_DEVIATION 11.56 |
| Sex: Female, Male Female | 21 Participants |
| Sex: Female, Male Male | 20 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk |
|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 41 | 1 / 38 |
| other Total, other adverse events | 28 / 41 | 33 / 41 | 32 / 38 |
| serious Total, serious adverse events | 5 / 41 | 6 / 41 | 13 / 38 |
Outcome results
Primary
Average Difference Between Morning and Non-Morning Log White Blood Cell (WBC) Cystine Values
The primary analysis of WBC cystine was performed using the natural log transformed WBC cystine level; the log transformation is a normalizing transformation. For each participant, the difference between the morning and corresponding non-morning log WBC cystine value (non-morning minus morning) at each monthly visit during the Cystagon® phase (Months 1, 2, and 3) was computed and these differences were averaged. The average difference between morning and non-morning log WBC cystine value was similarly computed for each participant during the RP103 phase (Months 5, 6, and 7). The primary analysis compared within-subject pairs (Cystagon® phase paired with RP103 phase) of non-morning minus morning average differences of log WBC cystine level.
Time frame: While taking Cystagon® (Months 1, 2, 3): within 15 minutes pre-morning (AM) and pre-non AM dose. During 3 months of RP103 (Months 5, 6, 7): 30 minutes post-AM and post-evening (PM) dose.
Population: Pharmacodynamic (PD) Analysis Set: All participants who received at least one treatment of Cystagon® and RP103 and who had at least one WBC cystine level recorded after each of Cystagon® treatment and RP103 treatment. Only participants with an average difference during both the Cystagon® and RP103 phases were included.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Cystagon® Phase | Average Difference Between Morning and Non-Morning Log White Blood Cell (WBC) Cystine Values | -0.229 log [nmol ½ cystine/mg protein] | Standard Deviation 0.5027 |
| RP103 Phase | Average Difference Between Morning and Non-Morning Log White Blood Cell (WBC) Cystine Values | 0.080 log [nmol ½ cystine/mg protein] | Standard Deviation 0.3939 |
p-value: 0.0048Paired t-test, two-sided
Secondary
Area Under the Plasma Concentration Time Curve From Time Point 0 Through the Last Measurable Point (AUC0-t) for Plasma Cysteamine
Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.
Time frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose
Population: PK Analysis Set: All participants who received at least one dose of RP103 and had available PK data at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cystagon® Phase | Area Under the Plasma Concentration Time Curve From Time Point 0 Through the Last Measurable Point (AUC0-t) for Plasma Cysteamine | Cystagon® dosing period | 7.8 hr*mg/L | Standard Deviation 5.18 |
| Cystagon® Phase | Area Under the Plasma Concentration Time Curve From Time Point 0 Through the Last Measurable Point (AUC0-t) for Plasma Cysteamine | RP103 dosing period | 9.4 hr*mg/L | Standard Deviation 4.86 |
Secondary
Halitosis Substudy: Expired Air DMS Concentrations
Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.
Time frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose 30 min post-dose, 2, 3, 4 and 6 hours post-dose. While taking RP103 (Month 4, 5, or 7): Within 15 min. prior to morning dose. 1, 2, 3, 4, 5, 6, 8, 10, 12 hours post dose
Population: PK Analysis Set: All participants who received at least one dose of RP103 and had available PK data at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | Cystagon®, 4 hours post morning dose | 8.8 nmol/L | Standard Deviation 12.05 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | Cystagon®, 6 hours post morning dose | 4.4 nmol/L | Standard Deviation 3.77 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | Cystagon®, within 15 minutes prior to dose | 4.7 nmol/L | Standard Deviation 5.54 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | Cystagon®, 30 minutes post dose | 4.7 nmol/L | Standard Deviation 4.75 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | Cystagon®, 1 hour post morning dose | 6.9 nmol/L | Standard Deviation 6.75 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | Cystagon®, 2 hours post morning dose | 11.9 nmol/L | Standard Deviation 11.26 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | Cystagon®, 3 hours post morning dose | 11.2 nmol/L | Standard Deviation 13.32 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, within 15 minutes prior to dose | 4.6 nmol/L | Standard Deviation 6.05 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 1 hour post morning dose | 5.4 nmol/L | Standard Deviation 7.71 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 2 hours post morning dose | 5.1 nmol/L | Standard Deviation 6.28 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 3 hours post morning dose | 7.7 nmol/L | Standard Deviation 8.53 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 4 hours post morning dose | 8.6 nmol/L | Standard Deviation 11.22 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 5 hours post morning dose | 11.2 nmol/L | Standard Deviation 15.86 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 6 hours post morning dose | 8.5 nmol/L | Standard Deviation 13.87 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 8 hours post morning dose | 5.7 nmol/L | Standard Deviation 10.76 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 10 hours post morning dose | 5.2 nmol/L | Standard Deviation 8.13 |
| Cystagon® Phase | Halitosis Substudy: Expired Air DMS Concentrations | RP103, 12 hours post morning dose | 4.3 nmol/L | Standard Deviation 5.32 |
Secondary
Halitosis Substudy: Maximum Plasma Concentration (Cmax) for Plasma Cysteamine
Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of dimethylsulfide (DMS) in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state pharmacokinetic (PK) samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.
Time frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose
Population: PK Analysis Set: All participants who received at least one dose of RP103 and had available PK data at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cystagon® Phase | Halitosis Substudy: Maximum Plasma Concentration (Cmax) for Plasma Cysteamine | Cystagon® dosing period | 3.5 mg/L | Standard Deviation 1.87 |
| Cystagon® Phase | Halitosis Substudy: Maximum Plasma Concentration (Cmax) for Plasma Cysteamine | RP103 dosing period | 2.9 mg/L | Standard Deviation 1.65 |
Secondary
Halitosis Substudy: Time to Cmax (Tmax) for Plasma Cysteamine
Participants who reported halitosis (bad breath) as a side effect while receiving Cystagon® were asked to participate in a substudy to investigate the concentration of DMS in expired air after the administration of study medication. To assess halitosis during study medication treatment, the steady state PK samples of cysteamine and DMS were collected over a 6 hour period when Cystagon® was administered and over a 12 hour period when RP103 was administered.
Time frame: While taking Cystagon® (Month 1, 2 or 3): Within 15 minutes prior to morning dose, 30 minutes post-dose, 1, 2, 4 and 6 hours post-dose. While taking RP103 (Month 5, 6, or 7): 30 minutes after morning dose and 1, 2, 3, 4, 6, 8, 10, 12 hours post-dose
Population: PK Analysis Set: All participants who received at least one dose of RP103 and had available PK data at given timepoint.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Cystagon® Phase | Halitosis Substudy: Time to Cmax (Tmax) for Plasma Cysteamine | Cystagon® dosing period | 1.2 hour | Standard Deviation 0.87 |
| Cystagon® Phase | Halitosis Substudy: Time to Cmax (Tmax) for Plasma Cysteamine | RP103 dosing period | 3.2 hour | Standard Deviation 1.3 |
Secondary
Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs
AE: any untoward medical occurrence that does not necessarily have a causal relationship with study drug. SAE: any untoward medical occurrence that at any dose: results in death; is life threatening; requires inpatient hospitalization or prolongation of existing hospitalization; results in persistent or significant disability or incapacity; is a congenital anomaly or birth defect; or is medically significant, and though not included in the above list, is an important medical event, according to the Investigator. Treatment-emergent adverse events (TEAEs) occurred after first dose of study drug. Clinically significant abnormalities in laboratory values (hematology, blood chemistry, urinalysis), electrocardiograms (ECGs), vital signs, and physical examinations were to be reported as adverse events and so are included in this summary of TEAEs
Time frame: From first dose of study drug to 7 days after last dose. Median duration of exposure was 91 days (range 82-108) for Cystagon® phase, 119 days (range 98-137) for the RP103 phase, and 861 days (range 30 - 1350) during the long-term RP-103 phase.
Population: Safety Analysis Set: all participants who received at least 1 dose of study drug (RP103). The row At least 1 TEAE includes both serious and non-serious AEs.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Cystagon® Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 serious TEAE | 5 Participants |
| Cystagon® Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE-related to study drug | 4 Participants |
| Cystagon® Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE | 31 Participants |
| Cystagon® Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 grade ≥ 3 TEAE | 5 Participants |
| Cystagon® Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE leading to discontinuation | 0 Participants |
| RP103 Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 grade ≥ 3 TEAE | 4 Participants |
| RP103 Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE-related to study drug | 20 Participants |
| RP103 Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE | 38 Participants |
| RP103 Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 serious TEAE | 6 Participants |
| RP103 Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE leading to discontinuation | 0 Participants |
| Long-Term Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE leading to discontinuation | 1 Participants |
| Long-Term Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 serious TEAE | 13 Participants |
| Long-Term Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE-related to study drug | 18 Participants |
| Long-Term Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 grade ≥ 3 TEAE | 13 Participants |
| Long-Term Phase | Number of Participants With Treatment-Emergent Adverse Events (AEs), Serious Adverse Events (SAEs), and Discontinuations Due to AEs | At least 1 TEAE | 32 Participants |