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

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ClinicalTrials.gov Identifier: NCT02741310
Recruitment Status : Completed
First Posted : April 18, 2016
Results First Posted : March 5, 2019
Last Update Posted : April 2, 2019
Sponsor:
Information provided by (Responsible Party):
Amgen

Brief 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.

Condition or disease Intervention/treatment Phase
Healthy Subjects Drug: Placebo Drug: Sumatriptan Drug: Erenumab Phase 1

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 34 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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
Actual Study Start Date : February 22, 2016
Actual Primary Completion Date : August 11, 2016
Actual Study Completion Date : August 11, 2016

Resource links provided by the National Library of Medicine

Drug Information available for: Sumatriptan

Arm Intervention/treatment
Placebo Comparator: Placebo
Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous sumatriptan on day 2 (Part 1). After a 2-day washout participants received another placebo IV infusion on day 4 followed by 12 mg subcutaneous sumatriptan on day 5 (Part 2).
Drug: Placebo
Administered by intravenous infusion

Drug: Sumatriptan
Administered by two 6 mg subcutaneous injections 1 hour apart on day 2 and day 5
Other Name: Imitrex™

Experimental: Erenumab
Participants received a placebo intravenous (IV) infusion on day 1 then 12 mg subcutaneous sumatriptan on day 2 (Part 1). After a 2-day washout participants received 140 mg erenumab IV infusion on day 4 followed by 12 mg subcutaneous sumatriptan on day 5 (Part 2).
Drug: Placebo
Administered by intravenous infusion

Drug: Sumatriptan
Administered by two 6 mg subcutaneous injections 1 hour apart on day 2 and day 5
Other Name: Imitrex™

Drug: Erenumab
Administered by intravenous infusion
Other Names:
  • AMG 334
  • Aimovig™




Primary Outcome Measures :
  1. Time-weighted Averages of Mean Arterial Pressure [ Time Frame: Days 2 and 5 from predose to 2.5 hours after sumatriptan dosing. ]

    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).



Secondary Outcome Measures :
  1. Number of Participants With Adverse Events [ Time Frame: 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. ]

    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.


  2. Area Under the Concentration-time Curve From Time 0 to 6 Hours for Sumatriptan [ Time Frame: 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. ]

    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).


  3. Area Under the Concentration-time Curve From Time 0 to Infinity for Sumatriptan [ Time Frame: 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. ]

    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).


  4. Maximum Observed Plasma Concentration (Cmax) of Sumatriptan [ Time Frame: 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. ]

    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).


  5. Number of Participants Who Developed Anti-erenumab Antibodies [ Time Frame: Baseline and day 89 ]

    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.




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Ages Eligible for Study:   18 Years to 55 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02741310


Locations
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Belgium
Research Site
Leuven, Belgium, 3000
Sponsors and Collaborators
Amgen
Investigators
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Study Director: MD Amgen

Additional Information:
Publications:
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Responsible Party: Amgen
ClinicalTrials.gov Identifier: NCT02741310     History of Changes
Other Study ID Numbers: 20140255
2015-004537-28 ( EudraCT Number )
First Posted: April 18, 2016    Key Record Dates
Results First Posted: March 5, 2019
Last Update Posted: April 2, 2019
Last Verified: March 2019

Additional relevant MeSH terms:
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Sumatriptan
Erenumab
Antibodies, Monoclonal
Vasoconstrictor Agents
Serotonin 5-HT1 Receptor Agonists
Serotonin Receptor Agonists
Serotonin Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Calcitonin Gene-Related Peptide Receptor Antagonists
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Immunologic Factors