Cluster Headache - Episodic and Chronic
Conditions
Keywords
Cluster Headache, Patient Diary collection of headache pain
Brief summary
The purpose of this study was to determine if SOM230 is safe and effective for the treament of cluster headache.
Detailed description
The purpose of this non-confirmatory study was to determine if SOM230 has adequate efficacy and safety to warrant further clinical development in cluster headache (CH). This study was a sequential design of SOM230 vs. Placebo.
Interventions
DRUGSOM230
The study evaluated SOM230 vs Placebo
DRUGPlacebo
The study evaluated SOM230 vs Placebo
Sponsors
Novartis Pharmaceuticals
Study design
Allocation
NON_RANDOMIZED
Intervention model
SEQUENTIAL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Caregiver)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Subject is male or female age 18-65 inclusive. * Written informed consent must be obtained before any assessment is performed. * Subjects must have established diagnosis of episodic cluster headaches (CH) or chronic CH, averaging 2-6 headache attacks per day each lasting at least 45 minutes without treatment, not to exceed 6 attacks per day within the last year. * Able to communicate well with the investigator, to understand and comply with the requirements of the study, as well as accepting NOT to share any study information through social media during their participation in the study. * Subject is able to self-inject medication subcutaneously or have the assistance of a partner on an out-patient basis.
Exclusion criteria
* Subjects that have a history of greater than 6 CH attacks per day within the last year. * Women of child-bearing potential, defined as all women physiologically capable of becoming pregnant, unless they are using effective methods of contraception during the duration dosing of the study treatment. Or men who are sexually active with women of child bearing potential, unless the male subjects always use condoms during the study. * History of multiple and recurring allergies or allergy to the investigational compound/compound class being used in this study. * Use of other investigational drugs at the time of enrollment, or within 5 half-lives of enrollment, or within 30 days, whichever is longer; or longer if required by local regulations. * A history of clinically significant heart diseases, ECG abnormalities, continued use of drugs known to prolong QTc during the study conduct, or any of the following ECG abnormalities at screening or baseline: * QTcF \> 450 msec (males) * QTcF \> 460 msec (females) * Uncontrolled diabetes as evidenced by screening HbA1c \> 8.0% * A positive Hepatitis B surface antigen or Hepatitis C test result. * A positive pregnancy test or lactating mothers. * History of drug or alcohol abuse within the 12 months prior to dosing other than prescription medications to manage their CH attacks, or evidence of such abuse as indicated by the laboratory assays conducted during screening. * Significant acute illness which has not resolved within two (2) weeks prior to initial dosing. * Any surgical or medical condition which might significantly jeopardize the subject's safety in case of participation in the study. The Investigator should make this determination in consideration of the subject's medical history and/or clinical or laboratory evidence of any of the following: * Liver disease or liver injury as indicated by abnormal liver function tests. ALT (SGPT), AST (SGOT), γ-GT, alkaline phosphatase and serum bilirubin will be tested. * ALT must be within the normal range * Serum bilirubin must not exceed 1.2 x ULN * γ-GT, AST and alkaline phosphatase must not exceed 2 x ULN \[If necessary, laboratory testing may be repeated on one occasion (as soon as possible) prior to treatment, to rule out any laboratory error\] * Acute cholecystitis or symptomatic cholelithiasis in subjects without H/O cholecystectomy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Headache Response (PD Analysis Set) | 30 minutes post dose | Defined as very severe, severe, or moderate pain before dosing that becomes mild or nil at 30 minutes post-dosing |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Were Pain Free at 30 Minutes Post Dose | 30 mins post dose | Participants who were pain free 30 minutes after dosing and reporting improvement of associated autonomic symptoms (for example, lacrimation, blushing, pupil constriction, etc.) over time was tabulated by dose. |
| Change in Hemoglobin Values From Screening to End of Study | screening and end of study, up to 9 days after treatment | Change in hemoglobin values from screening and end of study |
| Pulse Rate | screening and end of study, up to 9 days after treatment | Vital signs by treatment and time point |
Countries
Germany, United Kingdom, United States
Participant flow
Pre-assignment details
This study was planned to have 2 cohorts using a one-sequence two-period design to compare SOM230 vs. placebo. Two consecutive CH attacks were treated: the first attack was treated with placebo (Period 1) and the subsequent attack was treated with SOM230 (Period 2). However, Cohort 2 was not initiated.
Participants by arm
| Arm | Count |
|---|---|
| Placebo s.c. /1.5 mg SOM230 s.c. A: single dose of placebo s.c. (Period 1) B: single dose of 1.5 mg s.c. SOM230 (Period 2) | 28 |
| Total | 28 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Period 2 SOM230 - 2nd Attack | Physician Decision | 0 | 3 |
| Period 2 SOM230 - 2nd Attack | Protocol Violation | 0 | 1 |
Baseline characteristics
| Characteristic | Placebo s.c. /1.5 mg SOM230 s.c. |
|---|---|
| Age, Continuous | 43.9 Years STANDARD_DEVIATION 10.55 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 22 Participants |
| Sex: Female, Male Female | 6 Participants |
| Sex: Female, Male Male | 22 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 26 | 0 / 28 |
| other Total, other adverse events | 23 / 26 | 5 / 28 |
| serious Total, serious adverse events | 0 / 26 | 0 / 28 |
Outcome results
Primary
Number of Participants With Headache Response (PD Analysis Set)
Defined as very severe, severe, or moderate pain before dosing that becomes mild or nil at 30 minutes post-dosing
Time frame: 30 minutes post dose
Population: PD analysis set: Subjects with protocol deviations which impacted PD data were excluded from the PD analysis
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo s.c. | Number of Participants With Headache Response (PD Analysis Set) | 9 participants |
| SOM230 1.5 mg | Number of Participants With Headache Response (PD Analysis Set) | 10 participants |
p-value: 0.69890% CI: [0.419, 4.082]Regression, Logistic
Secondary
Change in Hemoglobin Values From Screening to End of Study
Change in hemoglobin values from screening and end of study
Time frame: screening and end of study, up to 9 days after treatment
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo s.c. | Change in Hemoglobin Values From Screening to End of Study | Screening | 153.4 g/L | Standard Deviation 12.93 |
| Placebo s.c. | Change in Hemoglobin Values From Screening to End of Study | End of Study | 149.5 g/L | Standard Deviation 15.13 |
Secondary
Number of Participants Who Were Pain Free at 30 Minutes Post Dose
Participants who were pain free 30 minutes after dosing and reporting improvement of associated autonomic symptoms (for example, lacrimation, blushing, pupil constriction, etc.) over time was tabulated by dose.
Time frame: 30 mins post dose
Population: PD analysis set)
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo s.c. | Number of Participants Who Were Pain Free at 30 Minutes Post Dose | 5 participants |
| SOM230 1.5 mg | Number of Participants Who Were Pain Free at 30 Minutes Post Dose | 7 participants |
p-value: 0.38590% CI: [0.53, 7.79]Regression, Logistic
Secondary
Pulse Rate
Vital signs by treatment and time point
Time frame: screening and end of study, up to 9 days after treatment
Population: Safety analysis set
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo s.c. | Pulse Rate | Screening | 77.2 Beats/min | Standard Deviation 15.02 |
| Placebo s.c. | Pulse Rate | Baseline | 78.1 Beats/min | Standard Deviation 11.99 |
| Placebo s.c. | Pulse Rate | Period 1 - Placebo | 76.9 Beats/min | Standard Deviation 12.77 |
| Placebo s.c. | Pulse Rate | Period 2 - SOM230 1.5 mg | 74.0 Beats/min | Standard Deviation 10.86 |
| Placebo s.c. | Pulse Rate | End of Study | 81.1 Beats/min | Standard Deviation 13.5 |