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Orvepitant (GW823296) in Adult Post Traumatic Stress Disorder

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01000493
First Posted: October 23, 2009
Last Update Posted: September 1, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Information provided by (Responsible Party):
GlaxoSmithKline
  Purpose

This is a 12-week, randomized, multicenter, double-blind, placebo controlled, fixed-dose parallel group study to assess the efficacy and safety of orvepitant (60 mg/day) versus placebo in subjects with a diagnosis of noncombat-related Posttraumatic Stress Disorder (PTSD), whose symptoms are considered moderate or severe.

Following an initial screening visit, subjects fulfilling the study inclusion and exclusion criteria will enter a pre-treatment screening phase to permit evaluation of the laboratory and ECG assessments and to confirm eligibility for inclusion into the study. This screening phase will be a minimum of 7 days, but no longer than 21 days. At the completion of the screening period, eligible subjects will be randomized at the baseline visit to receive either orvepitant 60mg/day or placebo (1:1 ratio). Those subjects randomized to receive placebo will receive study medication identical in appearance to that received by subjects assigned to receive orvepitant.

Efficacy will be assessed using the Clinician Administered PTSD Scale (CAPS) as the primary efficacy measure. Key secondary efficacy endpoints will be based on the Davidson Trauma Scale (DTS), the Short PTSD Rating Interview (SPRINT), the Clinical Global Impression- Global Improvement and Severity of Illness Scales (CGI-I and CGI-S, respectively), the Hamilton Depression Rating Scale (HAM-D), the Cognitive and Physical Functioning Questionnaire (CPFQ) and the Pittsburgh Sleep Quality Index (PSQI).

Safety will be assessed by monitoring for adverse events (side effects) and through periodic laboratory evaluations (blood tests), vital signs assessments (e.g., blood pressure, heart rate, temperature) and heart function measurements (electrocardiograms, or ECGs).


Condition Intervention Phase
Post-Traumatic Stress Disorder Drug: orvepitant Other: Placebo Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose Study Evaluating the Efficacy and Safety of the Neurokinin-1 Receptor Antagonist Orvepitant (GW823296) in Post Traumatic Stress Disorder (PTSD)

Resource links provided by NLM:


Further study details as provided by GlaxoSmithKline:

Primary Outcome Measures:
  • Change From Baseline in the 17-item Clinician Administered Posttraumatic Stress Disorder (PTSD) Scale (CAPS) Total Severity Score at Week 12 [ Time Frame: Baseline (Day 1 pre-dose) and Week 12 ]
    The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).


Secondary Outcome Measures:
  • Percentage of Participants Responding, Based on More Than Equal to (>=) 30 Percent (%) Reduction From Baseline in CAPS Total Severity Score at Weeks 1, 4, 8 and 12 [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. Percentage of participants were calculated by total number of responders divided by number of participants assessed multiplied by 100.

  • The Time to (Maintained) Clinical Response in Each Participants [ Time Frame: Up to Week 12 ]
    The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. The time required to maintain CAPS response has been summarized.

  • Change From Baseline in the 17-item CAPS Total Severity Score at Weeks 1, 4, and 8 [ Time Frame: Baseline (Day 1 pre-dose) and Week 1, 4, 8 ]
    The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Percentage of Participants Remitting, Based on a CAPS Total Score < 20 at Weeks 1, 4, 8, and 12 [ Time Frame: Up to Week 12 ]
    The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS total severity score was based on the 17 items that assess the frequency and intensity of PTSD symptoms. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The total score 0-136, higher scores means more severity, < 20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. Remitter defined as a participants who has a CAPS total score <20. Percentage of participants were calculated by total number of responders divided by number of participants assessed multiplied by 100.

  • Change From Baseline in the CAPS Re-experiencing Subscale Cluster Score at Weeks 1, 4, 8 and 12 [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS assessed Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV) diagnostic criteria for PTSD, including criteria B-D (core symptom clusters of re-experiencing). The re-experiencing subscale cluster score was derived from the CAPS. The possible range was 5 to 25 with lower score indicates less severe symptoms and with a greater score indicating greater PTSD symptom severity. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in the CAPS Avoidance/Numbing (A/N) Subscale Cluster Score at Weeks 1, 4, 8, and 12 [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS assessed DSM-IV diagnostic criteria for PTSD, including criteria B-D (core symptom clusters of A/N). The re-experiencing subscale cluster score was derived from the CAPS. The possible range is 7 to 35 with lower score indicates less severe symptoms and with a greater score indicating greater PTSD symptom severity. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in the CAPS Hyperarousal Subscale Cluster Score at Weeks 1, 4, 8, and 12 [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The CAPS was a 30-item clinical interview. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The CAPS assessed DSM-IV diagnostic criteria for PTSD, including criteria B-D (core symptom clusters of hyperarousal). The re-experiencing subscale cluster score was derived from the CAPS. The possible range is 5 to 25 with lower score indicates less severe symptoms and with a greater score indicating greater PTSD symptom severity. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Percentage of Participants Responding, Based on a Clinical Global Impression- Global Improvement (CGI-I) Score of 1 or 2, by Visit Week [ Time Frame: Up to Week 12 ]
    The global improvement items were rated on a 1-7 scale with 0 means not assessed (1: very much improved, 2: much improved, 3: minimally improved, 4: no change, 5: minimally worse, 6: much worse, 7: very much worse). For the global improvement item, the clinician indicated their assessment of the participant's total improvement or worsening compared with that individual's condition at the start of the study (the Baseline visit) whether or not the change was judged to be due to drug treatment. Responder was defined as a participant who had a CGI-I score of 1 or 2 ('very much improved' or 'much improved'). It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. Percentage of participants were calculated by total number of responders divided by number of participants assessed multiplied by 100.

  • Change From Baseline in the CGI-S Score, by Visit Week [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The severity of illness items were rated on a 1-7 scale with 0 means not assessed (1: normal, not at all ill, 2: borderline mentally ill, 3: mildly ill, 4: moderately ill, 5: markedly ill, 6: severely ill, 7: among the most extremely ill participants). For the severity of illness item, the clinician indicated his/her assessment of the participant severity of illness considering their total clinical experience with the particular population being studied. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in the Short PTSD Rating Review (SPRINT), by Visit Week [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The SPRINT consists of 8 items that assess the core symptoms of PTSD, as well as related aspects of somatic malaise, stress vulnerability and functional impairment. Each item was rated on a 5 point scale (0: not at all, 1: a little bit, 2: moderately, 3: quiet a lot and 4: very much), total score 0-32; with higher scores means more severity. Also, it provided the information about how the participant feeling (as a percentage) and symptoms improved since beginning of treatment (rated on a 5 point scale [0: worse, 1: a no change, 2: minimally, 3: much and 4: very much]). The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in the Self-rated Davidson Trauma Scale (DTS), by Visit Week [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    This instrument consists of 17 items which parallel the DSM criteria for PTSD. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) rated using 5-point scale. There were 8 items assessing associated features (guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment). The DTS cluster includes intrusion (items 1-4, 17 [score 0-40]), avoidance/numbing (A/N; items 5-11 [score 0-56]) and hyperarousal (items 12-16 [score 0-40]). The total score (0-136) was added, lower score indicates less symptoms and higher scores means more severity, <20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and > 80: extreme PTSD symptoms. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values.

  • Change From Baseline in the DTS Cluster Sub Score [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    This instrument consists of 17 items which parallel the DSM criteria for PTSD. Both frequency (0: never; 4: daily or all the time) and intensity (0: none or no problem; 4: extreme, incapacitating) rated using 5-point scale and added to get total score. There were 8 items including guilt, hopelessness, memory impairment, overall response validity, global PTSD severity, global improvement and social and occupational impairment. The DTS cluster includes intrusion (items 1-4, 17 [score 0-40]), A/N (items 5-11 [score 0-56]) and hyperarousal (items 12-16 [score 0-40]) with lower score indicates less symptoms and higher scores means more severity, <20: few symptoms or being asymptomatic, 20-39: mild or subthreshold PTSD, 40-59: threshold and moderate PTSD, 60-79: severe PTSD symptoms and >80: extreme PTSD symptoms. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in the Pittsburgh Sleep Quality Index (PSQI) Global Score, by Visit Week [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The PSQI was a self-rated questionnaire to assess sleep quality and disturbances. Individual items (19) generate 7-component scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication and daytime dysfunction. The global score generated by addition of individual score excluding use of sleeping medication component. It contains 15 objective (about frequency of sleep disturbances and subjective sleep quality) and 4 subjective (typical bedtime, wake-up time, sleep latency and sleep duration) items with score range from 0: no to 3: severe difficulty. The PSQI Global Score ranges from 0 to 21 and a global score > 5 was suggestive of significant sleep disturbance. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in the PSQI Addendum for PTSD (PSQI-A) Global Score, by Visit Week [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The PSQI-A was self-report instrument to assess disruptive nocturnal behavior (DNB) in PTSD participants with 7 types of DNB. These items include frequency of 1: hot flashes, 2: general nervousness, 3: memories or nightmares of traumatic experience, 4: severe anxiety or panic, not related to traumatic memories, 5: bad dreams, not related to traumatic memories, 6: episodes of terror or screaming during sleep without fully awakening and 7: episodes of acting out dreams, such as kicking, punching, running, or screaming. Each item was rated on a scale (0: not in the past month, 1: less than once a week, 2: once or twice a week and 3: three or more times a week) with global score range of 0-21. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in the CAPS Recurrent Distressing Dreams Item (B2) at Weeks 1, 4, 8, and 12 [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The B2 asked participant about 'Have you ever had unpleasant dreams about the event(s)? How often in the past month?' Both frequency (0: never; 4: daily or all the time) and 'at their worst, how much distress or discomfort did these dreams cause you? Did these dreams wake you up? [If yes, ask:] What were you feeling or doing when you awoke? How long does it usually take to get back to sleep? [Listen for report of panic symptoms, yelling, posturing] intensity (0: none or no problem with symptoms; 4: extreme, incapacitating) ratings were made on a 5-point scale. The total score 0-8, higher scores means more severity. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in Hamilton Depression Rating Scale (HAM-D), by Visit Week [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The HAM-D was observer-rated depressive symptom rating scale to measure the severity of depressive symptoms in participants with primary depressive illness. The items were ranked on a scale of 0-4 (0: absent; 4: greatest severity) or 0-2 (0: no difficulty; 2: difficulty falling asleep). In addition to the total score (0-66; with higher score indicates more depression), the HAM-D anxiety factor score (sum of items 10, 11, 12, 13, 15 and 17) and the melancholia subscore (sum of items 1, 2, 7, 8, 10, and 13) of the 17-item HAM-D scale was analyzed. The melancholia subscale was derived from three formal psychometric criteria (calibration, ascending monotonicity and dispersion). It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in the Cognitive and Physical Function Questionnaire (CPFQ) Total Score, by Visit Week [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The Massachusetts CPFQ was a brief self-report scale to measure cognitive and executive dysfunction in mood and anxiety disorders. The CPFQ comprises 7 questions assessing each of the most common complaints of depressed participants reporting fatigue or cognitive/executive problems. Each question was rated on a scale of 1 to 6, with 1: greater than normal, 2: normal, 3: minimally diminished, 4: moderately diminished, 5: markedly diminished and 6: totally absent functioning with total score 7-42; higher score indicating more dysfunction. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in Massachusetts Sexual Function Questionnaire (MSFQ) Total Score and Erectile Dysfunction Score in Males [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The MSFQ was derived from the Guided Interview Questionnaire for males and from the Arizona Sexual Experience Scale. The questionnaire includes five items with a score ranging from 1-6 (1: greater than normal; 2: normal; 3: minimally diminished; 4: moderately diminished; 5: markedly diminished and 6: totally absent with total score 5-30; higher score indicating more dysfunction). The areas of sexual functioning included were total score and erectile dysfunction (males only). A total score was used as a global measure of sexual dysfunction. A follow-up version of the questionnaire includes an additional sixth item of the participant's global impression of improvement, with a score ranging from 1 to 6. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in MSFQ Total Score in Females [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The MSFQ was derived from the Guided Interview Questionnaire for males and from the Arizona Sexual Experience Scale. The questionnaire includes five items with a score ranging from 1-6 (1: greater than normal; 2: normal; 3: minimally diminished; 4: moderately diminished; 5: markedly diminished and 6: totally absent with total score 5-30; higher score indicating more dysfunction). The areas of sexual functioning included were total score used as a global measure of sexual dysfunction. A follow-up version of the questionnaire includes an additional sixth item of the participant's global impression of improvement, with a score ranging from 1 to 6. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Change From Baseline in MSFQ Items (Diminished/Absent Libido; Arousal Difficulties; Orgasm Difficulties/Anorgasmia and Degree of Sexual Satisfaction) Scores [ Time Frame: Baseline (Day 1 pre-dose) and up to Week 12 ]
    The MSFQ was derived from the Guided Interview Questionnaire for males and from the Arizona Sexual Experience Scale. The questionnaire includes five items with a score ranging from 1-6 (1: greater than normal; 2: normal; 3: minimally diminished; 4: moderately diminished; 5: markedly diminished and 6: totally absent). The areas of sexual functioning included were diminished/absent libido; arousal difficulties; orgasm difficulties/anorgasmia and degree of sexual satisfaction. A follow-up version of the questionnaire includes an additional sixth item of the participant's global impression of improvement, with a score ranging from 1 to 6. It was assessed at Baseline, Week 1, 2, 4, 6, 8, 10 and 12. The change from Baseline was calculated by subtracting the Baseline values from the individual post-randomization values. Baseline was defined as value on Day 1 (pre-dose).

  • Number of Participant With Suicidal Behavior Based on the Columbia Suicide Severity Rating Scale (C-SSRS) During and Post Treatment [ Time Frame: Baseline, Week 1, 2, 4, 6, 8, 10, 12 and Day 14 of follow-up (approximately 14 weeks) ]
    The C-SSRS used to assess severity and change of suicidality by integrating both behavior and ideation and to be completed by the participants. The SSRS track change in the severity/density of suicidality. The interview was initiated with 5 (yes/no) questions; rated on 1-5 point scale, presented in ascending order of severity, about suicidal ideation. If the answers to the first 2 ideation questions were "yes," the clinician asked questions 3-5. If the answers to ideation questions 1 and 2 were "no," then the clinician proceeded to 5 (yes/no) questions that addressed suicidal behavior, which was categorized as actual attempt, engaged in non-suicidal self-injurious behavior, interrupted attempt, aborted attempt and preparatory acts or behaviors. Participants analyzed were number of participants with at least one C-SSRS assessment after the first dose of study medication (that is on treatment or post treatment).

  • Number of Participant by Maximum Suicidal Ideation, Based on the C-SSRS During and Post Treatment [ Time Frame: Baseline, Week 1, 2, 4, 6, 8, 10, 12 and Day 14 of follow-up (approximately 14 weeks) ]
    The C-SSRS used to assess severity and change of suicidality by integrating both behavior and ideation and to be completed by the participants. The SSRS track change in the severity/density of suicidality. It assessed intensity of ideation (a potentially important marker of severity), specifically asking about frequency, duration, intrusiveness, controllability, and deterrents. The interview was initiated with 5 (yes/no) questions; rated on 1-5 point scale, presented in ascending order of severity, about suicidal ideation. The clinician asked 5 questions: wish to be dead, non-specific active suicidal thoughts, active suicidal ideation without intent to act, active suicidal ideation with any methods (not plan) without intent to act and active suicidal ideation with specific plan and intent. Participants analyzed were number of participants with at least one C-SSRS assessment after the first dose of study medication (that is on treatment or post treatment).


Enrollment: 132
Actual Study Start Date: November 2, 2009
Study Completion Date: June 28, 2010
Primary Completion Date: June 28, 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Orvepitant 60 mg
60 mg/day
Drug: orvepitant
Neurokinin-1 (NK-1) antagonist
Other Name: GW823296
Placebo Comparator: Placebo Other: Placebo
Inactive placebo to match orvepitant 60 mg dosage form

Detailed Description:

The purpose of the current study is to test the safety and effects of orvepitant, an investigational drug for the treatment of noncombat-related PTSD.

Efficacy will be assessed using standard symptom and severity rating scales (questionnaires). The Clinicain Adminstered PTSD Scale (CAPS) will serve as the primary measure of efficacy. Secondary efficacy endpoints include the CAPS subscale clusters (Re-Experiencing, Avoidance and Numbing, and Hyperarousal), the Davidson Trauma Scale (DTS), the Short PTSD Rating Interview (SPRINT), the Hamilton Depression Rating Scale (HAM-D), the Clinical Global Impression- Global Improvement and Severity of Illness Scale (CGI-I and CGI-S, respectively), the Cognitive and Physical Functioning Questionnaire (CPFQ) and the Pittsburgh Sleep Quality Index (PSQI).

Safety and tolerability will be assessed by monitoring adverse events (AEs or side effects), physical examinations (including vital signs such as blood pressure and heart rate), clinical laboratory assessments (blood tests), electrical recordings of the heart (electrocardiograms or ECG's), the Columbia Suicidality Severity Rating Scale (CSSRS), Massachusetts Sexual Function Questionnaire (MSFQ), Discontinuation-Emergent Signs and Symptoms (DESS) scale and weight change.

Blood samples will be taken at different time points to assess blood levels of orvepitant in patients, allowing the relationship between amount of orvepitant in the body and efficacy to be studied.

The primary objective of the study is to evaluate the efficacy of orvepitant (60mg/day) versus placebo (a "sugar pill", with no active ingredients). The secondary objectives include assessing the safety and tolerability of orvepitant, assessing the profile of appearance and disappearance of orvepitant in the body (blood) following administration (i.e., assessing how long the drug remains in the body), and lastly to examine the relationship between blood levels of the drug and efficacy (i..e, the change in CAPS score relative to what it was before starting the study medication).

Following an initial screening visit, subjects fulfilling the study entrance criteria will enter a pre-treatment screening phase to permit evaluation of the laboratory and electrocardiogram assessments and to confirm eligibility for inclusion into the study. This screening phase will be a minimum of 7 days, but no longer than 21 days. Upon completion of the screening period, eligible subjects will be randomly assigned at the baseline visit to one of two treatment regimens: orvepitant 60mg/day or placebo for a 12-week treatment phase. The chances of receiving each of the two possible treatments will be equal. Orvepitant will be administered as tablets. Those subjects randomised to receive placebo will receive study medication identical in appearance to that received by subjects assigned to receive orvepitant.

During the treatment phase, subjects will be required to return to the clinic at the end of Weeks 1, 2, 4, 6, 8, 10 and 12. In addition, all subjects will be required to return for a follow-up visit 14 days after the last dose of study medication. In addition, all subjects with ongoing adverse events at the 14-day follow-up visit will be required to return for a further follow-up visit 28 days after the last dose of study medication. Women of child-bearing potential will also be required to attend the 28-Day follow-up visit for a pregnancy test. A further test will be performed 42 Days following the end of treatment.

Male and female outpatients between the ages of 18 to 64 years inclusive with a primary diagnosis of noncombat-related PTSD will be enrolled into this study. A total of approximately 240 subjects are expected to be enrolled at approximately 25 different study sites in North America.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years to 64 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Aged 18-64 years, inclusive.
  • A primary diagnosis of noncombat-related Post traumatic Stress Disorder (PTSD)
  • Subjects with symptom severity considered to be at least moderate to severe.

Exclusion Criteria:

  • Subjects whose symptoms are better accounted for by a diagnosis other than Post traumatic Stress Disorder (PTSD), subjects diagnosed with dementia; subjects diagnosed with a current/recent eating disorder such as anorexia nervosa or bulimia; subjects with a diagnosed history of schizophrenia, schizoaffective disorder, or Bipolar Disorder.
  • Subjects who have a history of failing to respond to adequate treatment for PTSD with an antidepressant/anti-anxiety drug, i..e, failure to improve following administration of at least two other antidepressants/anti-anxiety drugs, each given for at least 4 weeks.
  Contacts and Locations
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): NCT01000493


  Show 26 Study Locations
Sponsors and Collaborators
GlaxoSmithKline
Investigators
Study Director: GSK Clinical Trials GlaxoSmithKline
  More Information

Publications:
Responsible Party: GlaxoSmithKline
ClinicalTrials.gov Identifier: NCT01000493     History of Changes
Other Study ID Numbers: 113211
First Submitted: October 15, 2009
First Posted: October 23, 2009
Results First Submitted: March 31, 2017
Results First Posted: September 1, 2017
Last Update Posted: September 1, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by GlaxoSmithKline:
efficacy
double-blind
Clinician Administered PTSD Scale
placebo
Sleep
safety
CAPS
neurokinin-1 antagonist
orvepitant
PTSD
randomized
Post traumatic stress disorder
Phase II

Additional relevant MeSH terms:
Disease
Stress Disorders, Traumatic
Stress Disorders, Post-Traumatic
Pathologic Processes
Trauma and Stressor Related Disorders
Mental Disorders
Neurokinin A
Substance P
Neurokinin-1 Receptor Antagonists
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs