Sickle Cell Disease
Conditions
Keywords
Sickle Cell Disease, SCD, Olinciguat, IW-1701
Brief summary
The primary objective of the 1701-202 STRONG SCD study is to evaluate the safety and tolerability of different dose levels of IW-1701 compared with placebo when administered daily for approximately 12 weeks to patients with stable SCD. Exploratory objectives include evaluation of pharmacokinetic (PK) as well as evaluation of the effect of IW-1701 on symptoms of SCD, health-related quality of life, and biomarkers of pharmacodynamic (PD) activity.
Interventions
DRUGIW-1701
Oral Tablet
DRUGPlacebo
Oral Tablet
Sponsors
Cyclerion Therapeutics
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
16 Years to 70 Years
Healthy volunteers
No
Inclusion criteria
1. Patient is ambulatory male or female 16 to 70 years of age at the Screening Visit. 2. Patient has SCD, including homozygous hemoglobin S (HbSS), hemoglobin SC disease (HbSC), heterozygous hemoglobin S-beta zero (HbSβ0)-thalassemia, or heterozygous hemoglobin S-beta plus (HbSβ+)-thalassemia, documented in their medical history. 3. If patient is on medication(s) for SCD, such as hydroxyurea (HU), are on a stable regimen. 4. Per medical history and/or patient recall, patient has had at least 1 and no more than 10 sickle cell-related pain crises in the 12 months before the Screening Visit and none occurring in the 4 weeks before the Randomization Visit. 5. Patient completes daily eDiary entries for at least 10 days during the last 14 days of the Run in Period as assessed at the Randomization Visit. 6. Women of childbearing potential must have a negative pregnancy test prior to randomization and must agree to use protocol-specified contraception from the Screening Visit through 90 days after the final dose of study drug. 7. Male patients must be surgically sterile by vasectomy (conducted ≥60 days before the Screening Visit or confirmed via sperm analysis) or must agree to use protocol-specified contraception and agree to refrain from sperm donation from the Screening Visit through 90 days after the final dose of study drug.
Exclusion criteria
1. Patient requires a program of prescheduled, regularly administered chronic blood transfusion therapy. 2. Patient has been hospitalized for an SCD-related complication in the 4 weeks before the Randomization Visit. 3. Patient has taken opioid(s) \>200 morphine mg equivalent/day within the 4 weeks before the Randomization Visit. 4. Patient is taking aspirin ≥325 mg daily, P2Y12 inhibitors, any anticoagulant medication, specific inhibitors of phosphodiesterase 5 (PDE5), nonspecific inhibitors of phosphodiesterase 5 (PDE5), moderate or strong cytochrome P450 3A (CYP3A) inhibitors, any supplements for the treatment of erectile dysfunction, riociguat, or nitrates or nitric oxide donors in any form. 5. Patient has major concurrent illness or medical condition that in the opinion of the Investigator would preclude participation in a clinical study. NOTE: Other inclusion and
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups. | An adverse event (AE) is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. Adverse Events of special interest (AESIs) included symptomatic or Grade ≥2 hypotensive events and/or tachycardia AEs, bleeding events, pulmonary edema, and bone-related events, including fractures. |
| Double-Blind Treatment: Number of TEAE Events | First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups. | An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted. |
| Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups. | An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the most severe occurrence was counted. |
| Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs | First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups. | An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted. |
Countries
Lebanon, United Kingdom, United States
Participant flow
Pre-assignment details
After a 2-week single-blind placebo Run-in, eligible participants were stratified by hydroxyurea (hydroxycarbamide \[HU\]) use (yes or no) and randomly assigned to double-blind study drug (olinciguat or placebo). * Under Amendment 3 and earlier: Participants were assigned in a 1:1:1:1 ratio to placebo, 2 mg olinciguat, 4 mg olinciguat, or 6 mg olinciguat. * Under Amendment 4 and later: Participants were assigned in a 3:1 ratio to 18 mg olinciguat or placebo.
Participants by arm
| Arm | Count |
|---|---|
| Double-Blind Treatment: Placebo 1 Participants received placebo treatment QD for 12 weeks under the original protocol, Amendment 1, Amendment 2, and Amendment 3. | 9 |
| Double-Blind Treatment: Placebo 2 Participants received placebo treatment QD for 12 weeks under protocol Amendment 4 and later | 8 |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg Participants received 1 mg olinciguat QD Week 1 and 2 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3. | 8 |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg Participants received 2 mg olinciguat QD Week 1 and 4 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3. | 8 |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg Participants received 3 mg olinciguat QD Week 1 and 6 mg olinciguat QD Weeks 2-12 under the original protocol, Amendment 1, Amendment 2, and Amendment 3. | 11 |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg Participants received 6 mg olinciguat QD Days 1-7, 12 mg olinciguat QD Weeks 1-3, and 18 mg olinciguat QD Weeks 4-12 under protocol Amendment 4 and later. | 24 |
| Total | 68 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 | FG004 | FG005 | FG006 |
|---|---|---|---|---|---|---|---|---|
| Double-Blind Treatment Period | Adverse Event | 0 | 0 | 0 | 0 | 0 | 0 | 2 |
| Double-Blind Treatment Period | COVID-19 | 0 | 0 | 1 | 0 | 0 | 0 | 0 |
| Double-Blind Treatment Period | Lost to Follow-up | 0 | 1 | 0 | 0 | 2 | 0 | 0 |
| Double-Blind Treatment Period | Randomized Mistakenly During the Run-In Period - Did Not Receive Study Drug | 0 | 1 | 1 | 0 | 0 | 0 | 0 |
| Double-Blind Treatment Period | Withdrawal by Subject | 0 | 0 | 1 | 1 | 0 | 2 | 1 |
| Single-Blind Run-In Period | COVID-19 Pandemic Precautions - Suspended by Institutional Review Board (IRB) | 3 | 0 | 0 | 0 | 0 | 0 | 0 |
| Single-Blind Run-In Period | COVID-19 Pandemic Precautions- Suspended per Local Guidelines | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| Single-Blind Run-In Period | Physician Decision | 2 | 0 | 0 | 0 | 0 | 0 | 0 |
| Single-Blind Run-In Period | Protocol Violation | 11 | 0 | 0 | 0 | 0 | 0 | 0 |
| Single-Blind Run-In Period | Withdrawal by Subject | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
Baseline characteristics
| Characteristic | Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Total |
|---|---|---|---|---|---|---|---|
| Age, Continuous | 34.4 years STANDARD_DEVIATION 13.34 | 30.3 years STANDARD_DEVIATION 9.43 | 31.5 years STANDARD_DEVIATION 9.29 | 26.3 years STANDARD_DEVIATION 10.51 | 34.5 years STANDARD_DEVIATION 11.38 | 32.7 years STANDARD_DEVIATION 12.63 | 32.0 years STANDARD_DEVIATION 11.5 |
| Race/Ethnicity, Customized Black or African American | 10 Participants | 8 Participants | 4 Participants | 8 Participants | 8 Participants | 15 Participants | 53 Participants |
| Race/Ethnicity, Customized Hispanic or Latino | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 2 Participants |
| Race/Ethnicity, Customized Not Hispanic or Latino | 10 Participants | 7 Participants | 7 Participants | 6 Participants | 8 Participants | 22 Participants | 60 Participants |
| Race/Ethnicity, Customized Not Reported | 0 Participants | 0 Participants | 1 Participants | 1 Participants | 0 Participants | 0 Participants | 3 Participants |
| Race/Ethnicity, Customized Unknown | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 0 Participants | 1 Participants | 3 Participants |
| Race/Ethnicity, Customized White | 0 Participants | 0 Participants | 4 Participants | 0 Participants | 0 Participants | 9 Participants | 13 Participants |
| Sex: Female, Male Female | 6 Participants | 7 Participants | 5 Participants | 5 Participants | 7 Participants | 14 Participants | 44 Participants |
| Sex: Female, Male Male | 5 Participants | 2 Participants | 3 Participants | 3 Participants | 1 Participants | 10 Participants | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk | EG006 affected / at risk |
|---|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 88 | 0 / 9 | 0 / 8 | 0 / 8 | 0 / 8 | 0 / 11 | 0 / 24 |
| other Total, other adverse events | 18 / 88 | 6 / 9 | 6 / 8 | 5 / 8 | 5 / 8 | 6 / 11 | 20 / 24 |
| serious Total, serious adverse events | 2 / 88 | 2 / 9 | 1 / 8 | 2 / 8 | 3 / 8 | 4 / 11 | 6 / 24 |
Outcome results
Primary
Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity
An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the most severe occurrence was counted.
Time frame: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.
Population: Safety Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Any | 6 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 3 | 2 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 5 | 0 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 1 | 0 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 4 | 0 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 2 | 4 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 3 | 2 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 2 | 0 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 5 | 0 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 1 | 4 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Any | 6 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 4 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 3 | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Any | 5 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 1 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 2 | 3 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 5 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 4 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Any | 5 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 3 | 3 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 1 | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 5 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 2 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 4 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 3 | 4 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 1 | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Any | 8 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 4 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 5 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 2 | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Any | 21 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 3 | 7 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 1 | 6 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 5 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 4 | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With ≥1 TEAE, by Maximum Severity | Participants with ≥1 TEAE: Grade 2 | 8 Participants |
Primary
Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs
An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.
Time frame: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.
Population: Safety Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs | 3 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs | 4 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With Study Drug-Related TEAEs | 7 Participants |
Primary
Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs)
An adverse event (AE) is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. A serious AE (SAE) is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. Adverse Events of special interest (AESIs) included symptomatic or Grade ≥2 hypotensive events and/or tachycardia AEs, bleeding events, pulmonary edema, and bone-related events, including fractures.
Time frame: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.
Population: Safety Population: Randomized participants who received at least 1 dose of study drug
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE Leading to Study Drug Discontinuation | 0 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 SAE | 2 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE | 6 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 AESI | 0 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Study Drug-Related TEAE | 3 Participants |
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Grade 3-5 TEAE | 2 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Study Drug-Related TEAE | 0 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE Leading to Study Drug Discontinuation | 0 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE | 6 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 SAE | 1 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Grade 3-5 TEAE | 2 Participants |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 AESI | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE | 5 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Study Drug-Related TEAE | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 SAE | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE Leading to Study Drug Discontinuation | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 AESI | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Grade 3-5 TEAE | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE | 5 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 SAE | 3 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Study Drug-Related TEAE | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 AESI | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE Leading to Study Drug Discontinuation | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Grade 3-5 TEAE | 3 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Grade 3-5 TEAE | 4 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE Leading to Study Drug Discontinuation | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Study Drug-Related TEAE | 4 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 AESI | 0 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 SAE | 4 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE | 8 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE | 21 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 SAE | 6 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 AESI | 1 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Grade 3-5 TEAE | 7 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 TEAE Leading to Study Drug Discontinuation | 2 Participants |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of Participants With Treatment-Emergent Adverse Events (TEAEs) | Participants with >=1 Study Drug-Related TEAE | 7 Participants |
Primary
Double-Blind Treatment: Number of TEAE Events
An AE is any untoward medical occurrence that does not necessarily have to have a causal relationship with this treatment. An SAE is defined as any AE occurring at any dose that results in any of the following: death; life-threatening; hospitalization or prolongation of existing hospitalization; persistent or significant disability/incapacity; congenital anomaly/birth defect; other important medical event. A TEAE is an event that occurs after initiation of randomized study drug through 28 days after study drug discontinuation. Events were categorized by grade: 1=mild, 2=moderate, 3=severe, 4=life-threatening, 5=death, and as related or unrelated to study drug. If a participant had more than 1 occurrence in the same event category, only the occurrence with closest relationship to study drug was counted.
Time frame: First dose of randomized drug through 28 days after study drug discontinuation. Median number of weeks of treatment was 12.30, 11.85, 12.20, 12.20, 12.10, and 12.10, respectively, for Placebo 1, Placebo 2, Olinciguat 2 mg, 4 mg, 6 mg, and 18 mg groups.
Population: Safety Population: Randomized participants who received at least 1 dose of study drug. Participants with \>=1 TEAE.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Double-Blind Treatment: Placebo 1 | Double-Blind Treatment: Number of TEAE Events | 26 TEAE Events |
| Double-Blind Treatment: Placebo 2 | Double-Blind Treatment: Number of TEAE Events | 29 TEAE Events |
| Double-Blind Treatment: IW-1701 (Olinciguat) 2 mg | Double-Blind Treatment: Number of TEAE Events | 36 TEAE Events |
| Double-Blind Treatment: IW-1701 (Olinciguat) 4 mg | Double-Blind Treatment: Number of TEAE Events | 30 TEAE Events |
| Double-Blind Treatment: IW-1701 (Olinciguat) 6 mg | Double-Blind Treatment: Number of TEAE Events | 39 TEAE Events |
| Double-Blind Treatment: IW-1701 (Olinciguat) 18 mg | Double-Blind Treatment: Number of TEAE Events | 101 TEAE Events |