Trial Outcomes & Findings for Study to Evaluate the Effect of Erenumab on Blood Pressure When Given Concomitantly With Subcutaneous Sumatriptan (NCT NCT02741310)

Last Updated: 2019-04-02

Results Overview

Mean arterial pressure (MAP) is the average arterial pressure during a single cardiac cycle. MAP was calculated as diastolic blood pressure (DBP) + 0.33 \* (systolic blood pressure \[SBP\]-DBP). Individual time-weighted average in MAP were calculated as area under the measurement-time curve from predose through 2.5 hours of MAP divided by the time period over which the measurements were made (ie, AUCmap0-2.5 hr /2.5 hours). Data were analyzed using a linear mixed effects regression model with fixed effects for treatment and period and random effect for subject; Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

34 participants

Primary outcome timeframe

Days 2 and 5 from predose to 2.5 hours after sumatriptan dosing.

Results posted on

2019-04-02

Participant Flow

This study was conducted at 1 center in Belgium; participants were enrolled from 22 February 2016 to 11 May 2016.

Eligible participants were randomized on day 1 to receive either erenumab or matching placebo in a 2:1 allocation ratio.

Participant milestones

Participant milestones
Measure	Group A: Placebo + Sumatriptan Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous (SC) sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).	Group B: Erenumab + Sumatriptan Participants received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).
Overall Study STARTED	12	22
Overall Study COMPLETED	10	20
Overall Study NOT COMPLETED	2	2

Reasons for withdrawal

Reasons for withdrawal
Measure	Group A: Placebo + Sumatriptan Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous (SC) sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).	Group B: Erenumab + Sumatriptan Participants received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).
Overall Study Sponsor Decision	2	2

Baseline Characteristics

Study to Evaluate the Effect of Erenumab on Blood Pressure When Given Concomitantly With Subcutaneous Sumatriptan

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Group A: Placebo + Sumatriptan n=12 Participants Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous (SC) sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).	Group B: Erenumab + Sumatriptan n=22 Participants Participants received a placebo IV infusion on day 1 then 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan (6 mg, followed by 6 mg at least 1 hour later) on day 5 (Part 2).	Total n=34 Participants Total of all reporting groups
Age, Continuous	27.3 years STANDARD_DEVIATION 8.6 • n=5 Participants	29.1 years STANDARD_DEVIATION 10.3 • n=7 Participants	28.5 years STANDARD_DEVIATION 9.6 • n=5 Participants
Age, Customized 18 - 24 years	6 Participants n=5 Participants	9 Participants n=7 Participants	15 Participants n=5 Participants
Age, Customized 25 - 55 years	6 Participants n=5 Participants	13 Participants n=7 Participants	19 Participants n=5 Participants
Sex: Female, Male Female	4 Participants n=5 Participants	6 Participants n=7 Participants	10 Participants n=5 Participants
Sex: Female, Male Male	8 Participants n=5 Participants	16 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=5 Participants	22 Participants n=7 Participants	33 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Black (or African American)	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race/Ethnicity, Customized Multiple	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race/Ethnicity, Customized White	12 Participants n=5 Participants	21 Participants n=7 Participants	33 Participants n=5 Participants

PRIMARY outcome

Timeframe: Days 2 and 5 from predose to 2.5 hours after sumatriptan dosing.

Population: All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and with available data.

Outcome measures

Outcome measures
Measure	Sumatriptan Alone n=34 Participants All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	Erenumab + Sumatriptan n=20 Participants All participants who received erenumab plus sumatriptan (Group B, Part 2)	Part 2 Group A: Placebo + Sumatriptan In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.	Part 2 Group B: Erenumab + Sumatriptan In Part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.
Time-weighted Averages of Mean Arterial Pressure	87.40 mmHg Standard Error 0.98	87.36 mmHg Standard Error 1.22	—	—

SECONDARY outcome

Timeframe: From the first dose of study drug (sumatriptan, placebo or erenumab) until 84 days after the last dose (89 days). Part 1 includes AEs from day 1 to predose on day 4 and Part 2 includes AEs from day 4 through day 89.

Population: All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab).

Adverse events (AEs) were graded according to the Common Terminology Criteria for Adverse Events (CTCAE) version 4.0 and according to the following: Grade 1 = Mild AE, asymptomatic or mild symptoms; Grade 2 = Moderate, minimal, local or noninvasive intervention indicated; Grade 3 = Severe or medically significant but not immediately life-threatening; Grade 4 = Life-threatening consequences, urgent intervention indicated; Grade 5 = Death related to AE.

Outcome measures

Outcome measures
Measure	Sumatriptan Alone n=12 Participants All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	Erenumab + Sumatriptan n=22 Participants All participants who received erenumab plus sumatriptan (Group B, Part 2)	Part 2 Group A: Placebo + Sumatriptan n=12 Participants In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.	Part 2 Group B: Erenumab + Sumatriptan n=22 Participants In Part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.
Number of Participants With Adverse Events Any adverse event	11 Participants	19 Participants	9 Participants	17 Participants
Number of Participants With Adverse Events Adverse event ≥ grade 2	1 Participants	0 Participants	0 Participants	3 Participants
Number of Participants With Adverse Events Adverse event ≥ grade 3	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Adverse event ≥ grade 4	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Serious adverse events	0 Participants	0 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events AE leading to discontinuation of study drug	2 Participants	2 Participants	0 Participants	0 Participants
Number of Participants With Adverse Events Fatal adverse events	0 Participants	0 Participants	0 Participants	0 Participants

SECONDARY outcome

Timeframe: Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.

Population: All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter.

Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Area under the plasma concentration-time curve from time 0 to 6 hours post dose (AUC6hr) after the 2nd 6 mg dose of sumatriptan was estimated using the linear trapezoidal method. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ; 0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUC6hr was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).

Outcome measures

Outcome measures
Measure	Sumatriptan Alone n=30 Participants All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	Erenumab + Sumatriptan n=20 Participants All participants who received erenumab plus sumatriptan (Group B, Part 2)	Part 2 Group A: Placebo + Sumatriptan In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.	Part 2 Group B: Erenumab + Sumatriptan In Part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.
Area Under the Concentration-time Curve From Time 0 to 6 Hours for Sumatriptan	133.33 hr*ng/mL Standard Error 1.03	130.59 hr*ng/mL Standard Error 1.04	—	—

SECONDARY outcome

Timeframe: Day 2 and day 5 at 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.

Population: All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter.

Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. The area under the plasma concentration-time curve from time 0 to infinity (AUCinf) after the 2nd 6 mg dose of sumatriptan was estimated as the sum of AUClast and Clast/λz where Clast is the last observed concentration and λz is the first-order terminal rate constant estimated via linear regression of the terminal log-linear decay phase. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed AUCinf was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).

Outcome measures

Outcome measures
Measure	Sumatriptan Alone n=30 Participants All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	Erenumab + Sumatriptan n=20 Participants All participants who received erenumab plus sumatriptan (Group B, Part 2)	Part 2 Group A: Placebo + Sumatriptan In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.	Part 2 Group B: Erenumab + Sumatriptan In Part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.
Area Under the Concentration-time Curve From Time 0 to Infinity for Sumatriptan	144.32 hr*ng/mL Standard Error 1.03	144.81 hr*ng/mL Standard Error 1.04	—	—

SECONDARY outcome

Timeframe: Day 2 and day 5 at predose, 1 hour (prior to 2nd sumatriptan injection), 1 hour 10 minutes, 1.25, 1.5, 2, 3, 4.5, and 7 hours relative to the first 6 mg dose of sumatriptan.

Population: All participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) and have at least one pharmacokinetic (PK) sample collected or one PK parameter.

Plasma concentrations of sumatriptan were quantified using a validated high performance liquid chromatographic method with tandem mass spectrometry detection. Sumatriptan plasma concentrations below the lower limit of quantification (LLOQ) (0.100 ng/mL) were set to 0 before data analysis. Log-transformed maximum observed plasma concentration (Cmax) was analyzed using a linear mixed effects model with treatment as a fixed effect and subject as a random effect. Sumatriptan Alone data include participants from both Groups A (Parts 1 and 2) and B (Part 1 only).

Outcome measures

Outcome measures
Measure	Sumatriptan Alone n=30 Participants All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	Erenumab + Sumatriptan n=20 Participants All participants who received erenumab plus sumatriptan (Group B, Part 2)	Part 2 Group A: Placebo + Sumatriptan In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.	Part 2 Group B: Erenumab + Sumatriptan In Part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.
Maximum Observed Plasma Concentration (Cmax) of Sumatriptan	83.50 ng/mL Standard Error 1.05	79.00 ng/mL Standard Error 1.07	—	—

SECONDARY outcome

Timeframe: Baseline and day 89

Population: Participants who received at least 1 dose of study drug (placebo, sumatriptan, or erenumab) with a postbaseline antibody result.

Two validated assays were used to detect the presence of anti-erenumab antibodies. All samples were first tested in an electrochemiluminescence-based bridging assay to detect antibodies capable of binding to erenumab (Binding Antibody Assay). Samples confirmed to be positive for binding antibodies were subsequently tested in a cell-based assay to determine neutralizing activity against erenumab (Neutralizing Antibody Assay). If a post-dose sample was positive for binding antibodies and demonstrated neutralizing activity at the same time point, the sample was defined as positive for neutralizing antibodies. Binding/neutralizing antibody positive is defined as participants with an antibody positive postbaseline results and with a negative or no result at baseline.

Outcome measures

Outcome measures
Measure	Sumatriptan Alone n=10 Participants All participants who received placebo and sumatriptan (Group A, Parts 1 and 2 and Group B, Part 1).	Erenumab + Sumatriptan n=20 Participants All participants who received erenumab plus sumatriptan (Group B, Part 2)	Part 2 Group A: Placebo + Sumatriptan In Part 2 participants in Group A received another placebo IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.	Part 2 Group B: Erenumab + Sumatriptan In Part 2 participants in Group B received 140 mg erenumab IV infusion on day 4 followed by 12 mg SC sumatriptan on day 5.
Number of Participants Who Developed Anti-erenumab Antibodies Binding antibody positive	0 Participants	1 Participants	—	—
Number of Participants Who Developed Anti-erenumab Antibodies Neutralizing antibody positive	0 Participants	1 Participants	—	—

Adverse Events

Part 1 Group A: Placebo + Sumatriptan

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Part 1 Group B: Placebo + Sumatriptan

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Part 2 Group A: Placebo + Sumatriptan

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Part 2: Group B: Erenumab + Sumatriptan

Serious events: 0 serious events

Other events: 17 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Additional Information

Study Director

Amgen Inc.

Phone: 866-572-6436

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Clinical Trial Agreement generally does not restrict an investigator's discussion of trial results after completion. The Agreement permits Amgen a limited period of time to review material discussing trial results (typically up to 45 days and possible extension). Amgen may remove confidential information, but authors have final control and approval of publication content. For multicenter studies, the investigator agrees not to publish any results before the first multi-center publication.
Publication restrictions are in place

Restriction type: OTHER