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

Healthy Subjects Clinical Trial

Official title:

Phase 1, Randomized, Parallel-Group, Double-Blind, Placebo-Controlled, Single-Dose Study to Evaluate the Effect on Blood Pressure of AMG 334 Given Concomitantly With Subcutaneous Sumatriptan (Imitrex™) in Healthy Subjects

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02741310
• Other study ID #: 20140255
• Secondary ID: 2015-004537-28
• Status: Completed
• Phase: Phase 1
• Start date: February 22, 2016
• Est. completion date: August 11, 2016

Study information

• Verified date: March 2019
• Source: Amgen
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The primary objective of this study was to assess the effects of subcutaneous sumatriptan alone and the effects of a single dose of erenumab (AMG 334) intravenous (IV) and sumatriptan concomitant therapy on resting blood pressure in healthy adults.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 34
• Est. completion date: August 11, 2016
• Est. primary completion date: August 11, 2016
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 55 Years

Eligibility

Inclusion Criteria:

• Healthy male and female subjects = 18 to = 55 years old

• Good general health

• Laboratory results within range

• Other Inclusion Criteria May Apply

Exclusion Criteria:

• Female subjects pregnant or breastfeeding

• An unstable medical condition

• History of cancer

• Active liver disease

• Positive Hepatitis B or Hepatitis C

• Unwilling or unable to limit alcohol consumption

• Unable to refrain from strenuous exercise

• Other Exclusion Criteria May Apply

Related Conditions & MeSH terms

• Healthy Subjects

Intervention

Drug:
• Placebo
Administered by intravenous infusion
• Sumatriptan
Administered by two 6 mg subcutaneous injections 1 hour apart on day 2 and day 5
• Erenumab
Administered by intravenous infusion

Locations

Country	Name	City	State
Belgium	Research Site	Leuven

Sponsors (1)

Lead Sponsor	Collaborator
Amgen

Country where clinical trial is conducted

Belgium, 

References & Publications (1)

de Hoon J, Van Hecken A, Vandermeulen C, Herbots M, Kubo Y, Lee E, Eisele O, Vargas G, Gabriel K. Phase 1, randomized, parallel-group, double-blind, placebo-controlled trial to evaluate the effects of erenumab (AMG 334) and concomitant sumatriptan on blood pressure in healthy volunteers. Cephalalgia. 2019 Jan;39(1):100-110. doi: 10.1177/0333102418776017. Epub 2018 May 21. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Time-weighted Averages of Mean Arterial Pressure	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).	Days 2 and 5 from predose to 2.5 hours after sumatriptan dosing.
Secondary	Number of Participants With Adverse Events	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.	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.
Secondary	Area Under the Concentration-time Curve From Time 0 to 6 Hours for Sumatriptan	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).	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.
Secondary	Area Under the Concentration-time Curve From Time 0 to Infinity for Sumatriptan	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/?z where Clast is the last observed concentration and ?z 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).	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.
Secondary	Maximum Observed Plasma Concentration (Cmax) of Sumatriptan	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).	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.
Secondary	Number of Participants Who Developed Anti-erenumab Antibodies	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.	Baseline and day 89

External Links

•   AmgenTrials clinical trials website