Randomized, Double-Blind, Placebo Controlled Study of Vilazodone's Efficacy, Safety, and Biomarkers of Response in Major Depressive Disorder (MDD)

• Sponsor: Forest Laboratories (Industry)
• Overall Status: Completed
• CT.gov ID: NCT00683592
• Collaborator: (none)
• Enrollment: 481
• Locations: 9
• Arms: 2
• Duration (Months): 12
• Patients Per Site: 53.4
• Patients Per Site Per Month: 4.5

Study Details

Study Description

Brief Summary

This randomized, double-blind, placebo-controlled, multicenter, 8-week, clinical trial is designed to assess the efficacy and safety of vilazodone and to evaluate genetic biomarkers of treatment response associated with vilazodone use in adult patients diagnosed with MDD by the DSM-IV-TR criteria.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: vilazodone; Drug: placebo	Phase 3

Detailed Description

This randomized, double-blind, placebo-controlled, multicenter, 8-week, clinical trial is designed to assess the efficacy and safety of vilazodone and to evaluate genetic biomarkers of treatment response associated with vilazodone use in adult patients diagnosed with MDD by the DSM-IV-TR criteria. This study will enroll approximately 470 patients at approximately 10 clinical sites. Safety and efficacy will be assessed at each visit. A DNA sample will be collected and analyzed for response to vilazodone.

Study Design

• Study Type: Interventional
• Actual Enrollment: 481 participants
• 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 Study Assessing the Efficacy and Safety of Vilazodone 40 mg qd and Evaluating Genetic Biomarkers Associated With Treatment Response in Patients With Major Depressive Disorder (MDD)
• Study Start Date: Mar 1, 2008
• Actual Primary Completion Date: Feb 1, 2009
• Actual Study Completion Date: Mar 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 vilazodone	Drug: vilazodone; titration to 40 mg tablets qd (once a day) for 8 weeks; Other Names: EMD68843, SB-659746
Placebo Comparator: 2	Drug: placebo; placebo

Outcome Measures

Primary Outcome Measures

1. Change From Baseline to Week 8 in the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score. [Baseline, Week 1, Week 2, Week 4, Week 6, Week 8]

   The MADRS is an observer rating scale that has proven to be an efficient and practical measure of depression. The scale was constructed to be sensitive to treatment effects. The change from baseline in MADRS total score has a possible range of -60 to 60 where negative values reflect improvement in depression symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.

Secondary Outcome Measures

1. Change From Baseline to Week 8 in the HAM-D 17 (17-Item Hamilton Rating Scale for Depression) Total Score [Baseline, week 1, week 2, week 4, week 6, week 8]

   The HAM-D 17 is a 17-item subscale of the HAM-D 21, which is designed to be completed by a trained rater. It is designed for rating depressive symptom severity in patients with a confirmed diagnosis of depressive disorder. The change in HAM-D 17 has a possible range of -52 to 52 with negative values indicating improvment in depression symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.

2. The CGI-I (Clinician's Global Impression of Improvement) Score at Week 8 [Week 1, Week 2, Week 4, Week 6, Week 8]

   The CGI-I scale measures change from the baseline state at every visit after the baseline visit. It permits a global evaluation of the patient's improvement over time. At the scheduled clinic visits, the clinician assessed the patient's improvement relative to the symptoms at baseline on a CGI-I item using a 7-point scale, where 1 = very much improved and 7 = very much worse. The method of last observation carried forward was utilized for subjects who discontinued prematurely.

3. Change From Baseline to Week 8 in the HAM-A ( Hamilton Anxiety Rating Scale) Total Score [Baseline, Week 1, Week 2, Week 4, Week 6, Week 8]

   The HAM-A is a rating scale developed to quantify the severity of anxiety. It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe). Change from baseline in the HAM-A total score may range from -52 to 52 with negative value indicating improvement in anxiety symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.

4. MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate at Week 8 [Baseline, Week 1, Week 2, Week 4, Week 6, Week 8]

   MADRS response was defined as ≥ 50% decrease from baseline in MADRS total score at Week 8. The response rate is the percentage of subjects in each treatment group meeting the criteria for response. The method of last observation carrier forward was utilized for subjects who discontinued prematurely.

5. MADRS (Montgomery-Asberg Depression Rating Scale) Remission Rate at Week 8 [Baseline, Week 1, Week 2, Week 4, Week 6, Week 8]

   MADRS remission was defined as a MADRS total score < 10 at Week 8. The remission rate is the percentage of subjects in each treatment group who met the criteria for remission. The method of last observation carried forward was utilized for subjects who discontinued prematurely.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 70 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patients 18-70 years of age.

• A diagnosis of MDD, single episode or recurrent, according to DSM-IV-TR (296.2/296.3) with a current Major Depressive Episode of less than two year's duration with a minimum duration of at least 4 weeks.

• Meets DSM-IV-TR criteria for Major Depressive Disorder.

• HAM-D score ≥ 22 on the first 17 items of the 21-item HAM-D.

• HAM-D item 1 (depressed mood) score ≥ 2.

• Patients must be able to provide written informed consent

• Patients must be able to speak, read and understand English

Exclusion Criteria:

• Patients with a current (or within 6 months prior to the Screening Visit) Axis I disorder of Post Traumatic Stress Disorder, Eating Disorder, Obsessive Compulsive Disorder.

• Patients with a history of schizophrenia, schizoaffective disorder or bipolar I or II disorder (with a history of hypomanic or manic episodes).

• Patients who meet DSM-IV-TR criteria for substance abuse (alcohol or drugs) within 3 months prior to the Screening Visit or substance dependence within 6 months prior to the Screening Visit.

• Patients who meet criteria for any of the following DSM-IV-TR MDD Specifiers: [a] With Catatonic Features; [b] With Postpartum Onset; [c] With Seasonal Pattern [d]severe with Psychotic Features.

• Patients who are receiving formal psychotherapy or have had psychotherapy within the 12 weeks prior to the Screening Visit.

• Patients who have any one of the following:

• In the month prior to screening, have had active suicidal ideation with some intent to act, without specific plan.

• In the month prior to screening, have had suicidal ideation with specific plan and intent.

• Have made a suicide attempt within the 6 months prior to the screening visit.

• In the opinion of the Investigator, is currently at significant risk of suicide.

• Patients who have had an inadequate response to at least 2 consecutive antidepressants from different classes given at adequate doses for an adequate duration.

• Patients who have received electroconvulsive therapy within the 6 months prior to the Screening Visit.

• Patients currently taking a psychotropic drug. Patients who have taken psychotropic drugs must have discontinued these prior to the Screening Visit. The minimum discontinuation periods are outlined in the study protocol.

• Patients taking migraine medications with a serotonergic mechanism of action

• Patients taking CYP3A4 inhibitors such as grapefruit juice, ketoconazole, diltiazem, and macrolide antibiotics or montelukast

• Patients with known hypersensitivity to SSRIs (selective serotonin reyptake inhibitors) or 5-HT1a agonists.

• Patients previously treated with vilazodone (also known as SB-659746-A or EMD 68 843).

• Patients with a history of clinically significant cardiac, renal, neurologic, cerebrovascular, hepatic, hematologic, metabolic or pulmonary disorders.

• Patients with any serious medical disorder or condition that would, in the investigator's opinion, preclude the administration of study medication.

• Female patients must not be pregnant, lactating, or planning to become pregnant during the time of study participation. All female patients must be at least 1 year post menopausal or irreversibly surgically sterilized (by hysterectomy, oophorectomy, or bilateral tubal ligation with resection) or determined not to be at risk of pregnancy.

• Patients with clinically significant abnormalities on electrocardiogram.

• Patients having clinically significant abnormal laboratory findings.

• Patients with a positive drug screen.

• Patients who, in the opinion of the investigator, would be noncompliant with the visit schedule or study procedures.

• Patients that have taken an investigational drug or participated in an investigational drug trial within the past 30 days.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Pharmacology Research Institute	Newport Beach	California	United States	92660
2	Florida Clinical Research Center	Bradenton	Florida	United States	34208
3	Atlanta Institute of Medicine and Research	Atlanta	Georgia	United States	30328
4	Summit Research Network	Portland	Oregon	United States	97210
5	University of Pennsylvania Department of Psychiatry Mood and Anxiety Disorders	Philadelphia	Pennsylvania	United States	19104
6	Mood Disorders Research Program and Clinic Exchange Park	Dallas	Texas	United States	75235
7	University of Utah Health Sciences Ctr, Dept of Psychiatry Mood Disorders Clinic	Salt Lake City	Utah	United States	84132
8	Northwest Clinical Research Center	Bellevue	Washington	United States	98004
9	Summit Research Network	Seattle	Washington	United States	98104

Sponsors and Collaborators

• Forest Laboratories

Investigators

• Study Director: Carol R Reed, MD, Forest Laboratories

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00683592
• Other Study ID Numbers: CLDA-07-DP-02
• First Posted: May 23, 2008
• Last Update Posted: Oct 27, 2010
• Last Verified: Oct 1, 2010

• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Vilazodone Hydrochloride

Study Results

Participant Flow

Recruitment Details	Recruitment period was 31Mar2008 to 10Feb2009.
Pre-assignment Detail	This study included a washout period to allow patients to discontinue their current antidepressant medications and any additional medications prohibited by the protocol, if applicable.

Arm/Group Title	Vilazodone	Placebo
Arm/Group Description	Vilazodone titrated to 40mg. Two tablets per day.	Placebo to match vilazodone. Two tablets per day.
Period Title: Overall Study
STARTED	240	241
Intent to Treat Population	231	232
Safety Population	235	233
COMPLETED	193	195
NOT COMPLETED	47	46

Baseline Characteristics

Arm/Group Title	Vilazodone (ITT Population)	Placebo (ITT Population)	Total
Arm/Group Description	Vilazodone, 40 mg	placebo to match vilazodone	Total of all reporting groups
Overall Participants	231	232	463
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.1 (12.22)	42.4 (12.49)	41.7 (12.36)
Sex: Female, Male (Count of Participants)
Female	138 59.7%	123 53%	261 56.4%
Male	93 40.3%	109 47%	202 43.6%
Region of Enrollment (participants) [Number]
United States	231 100%	232 100%	463 100%

Outcome Measures

1. Primary Outcome

Title	Change From Baseline to Week 8 in the MADRS (Montgomery-Asberg Depression Rating Scale) Total Score.
Description	The MADRS is an observer rating scale that has proven to be an efficient and practical measure of depression. The scale was constructed to be sensitive to treatment effects. The change from baseline in MADRS total score has a possible range of -60 to 60 where negative values reflect improvement in depression symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame	Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.

Arm/Group Title	Vilazodone (ITT Population)	Placebo (ITT Population)
Arm/Group Description	Vilazodone, 40 mg	placebo to match vilazodone
Measure Participants	231	231
Least Squares Mean (95% Confidence Interval) [Units on a scale]	-13.3	-10.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vilazodone (ITT Population), Placebo (ITT Population)
	Comments	The model was an analysis of covariance (ANCOVA), with terms for treatment group and center, adjusting for baseline MADRS total score. Missing values at week 8 were handled using the last observation carried forward (LOCF) approach.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.009
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean Change
	Estimated Value	-2.5
	Confidence Interval	(2-Sided) 95%; -4.4 to -0.6
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Change From Baseline to Week 8 in the HAM-D 17 (17-Item Hamilton Rating Scale for Depression) Total Score
Description	The HAM-D 17 is a 17-item subscale of the HAM-D 21, which is designed to be completed by a trained rater. It is designed for rating depressive symptom severity in patients with a confirmed diagnosis of depressive disorder. The change in HAM-D 17 has a possible range of -52 to 52 with negative values indicating improvment in depression symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame	Baseline, week 1, week 2, week 4, week 6, week 8

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.

Arm/Group Title	Vilazodone (ITT Population)	Placebo (ITT Population)
Arm/Group Description	Vilazodone, 40 mg	placebo to match vilazodone
Measure Participants	231	231
Least Squares Mean (95% Confidence Interval) [Units on a scale]	-10.7	-9.1

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vilazodone (ITT Population), Placebo (ITT Population)
	Comments	The model was an analysis of covariance (ANCOVA), with terms for treatment group and center, adjusting for baseline HAM-D 17 total score. Missing values at week 8 were handled using the last observation carried forward (LOCF) approach.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.026
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean Change
	Estimated Value	-1.6
	Confidence Interval	(2-Sided) 95%; -3.1 to -0.2
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	The CGI-I (Clinician's Global Impression of Improvement) Score at Week 8
Description	The CGI-I scale measures change from the baseline state at every visit after the baseline visit. It permits a global evaluation of the patient's improvement over time. At the scheduled clinic visits, the clinician assessed the patient's improvement relative to the symptoms at baseline on a CGI-I item using a 7-point scale, where 1 = very much improved and 7 = very much worse. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame	Week 1, Week 2, Week 4, Week 6, Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.

Arm/Group Title	Vilazodone (ITT Population)	Placebo (ITT Population)
Arm/Group Description	Vilazodone, 40 mg	placebo to match vilazodone
Measure Participants	231	231
Least Squares Mean (95% Confidence Interval) [Units on a scale]	2.5	2.8

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vilazodone (ITT Population), Placebo (ITT Population)
	Comments	The model was an analysis of variance (ANOVA), with terms for treatment group and center. Missing values at week 8 were handled using the last observation carried forward (LOCF) approach.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.004
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean Improve
	Estimated Value	-0.3
	Confidence Interval	(2-Sided) 95%; -0.5 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change From Baseline to Week 8 in the HAM-A ( Hamilton Anxiety Rating Scale) Total Score
Description	The HAM-A is a rating scale developed to quantify the severity of anxiety. It consists of 14 items, each defined by a series of symptoms. Each item is rated on a 5-point scale, ranging from 0 (not present) to 4 (severe). Change from baseline in the HAM-A total score may range from -52 to 52 with negative value indicating improvement in anxiety symptom severity. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame	Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.

Arm/Group Title	Vilazodone (ITT Population)	Placebo (ITT Population)
Arm/Group Description	Vilazodone, 40 mg	placebo to match vilazodone
Measure Participants	231	231
Least Squares Mean (95% Confidence Interval) [Units on a scale]	-7.0	-5.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vilazodone (ITT Population), Placebo (ITT Population)
	Comments	The model was an analysis of covariance (ANCOVA), with terms for treatment group and center, adjusting for baseline HAM-A total score. Missing values at week 8 were handled using the last observation carried forward (LOCF) approach.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.037
	Comments
	Method	ANCOVA
	Comments
Method of Estimation	Estimation Parameter	Difference in Least Squares Mean Change
	Estimated Value	-1.2
	Confidence Interval	(2-Sided) 95%; -2.4 to -0.1
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	MADRS (Montgomery-Asberg Depression Rating Scale) Response Rate at Week 8
Description	MADRS response was defined as ≥ 50% decrease from baseline in MADRS total score at Week 8. The response rate is the percentage of subjects in each treatment group meeting the criteria for response. The method of last observation carrier forward was utilized for subjects who discontinued prematurely.
Time Frame	Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.

Arm/Group Title	Vilazodone (ITT Population)	Placebo (ITT Population)
Arm/Group Description	Vilazodone, 40 mg	placebo to match vilazodone
Measure Participants	231	231
Number [Participants]	101 43.7%	70 30.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vilazodone (ITT Population), Placebo (ITT Population)
	Comments	Cochran-Mantel-Haenszel tests were used to compare MADRS response rates between the treatment groups, stratifying by center. The asymptotic confidence interval of the risk difference was estimated by the normal approximation to the binomial distribution.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.002
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.134
	Confidence Interval	(2-Sided) 95%; 0.047 to 0.221
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	MADRS (Montgomery-Asberg Depression Rating Scale) Remission Rate at Week 8
Description	MADRS remission was defined as a MADRS total score < 10 at Week 8. The remission rate is the percentage of subjects in each treatment group who met the criteria for remission. The method of last observation carried forward was utilized for subjects who discontinued prematurely.
Time Frame	Baseline, Week 1, Week 2, Week 4, Week 6, Week 8

Outcome Measure Data

Analysis Population Description

Intent-to-Treat (ITT): the ITT population consisted of patients who were randomized, took at least 1 dose of study drug, and had at least 1 post-baseline efficacy endpoint measurement.

Arm/Group Title	Vilazodone (ITT Population)	Placebo (ITT Population)
Arm/Group Description	Vilazodone, 40 mg	placebo to match vilazodone
Measure Participants	231	231
Number [Participants]	63 27.3%	47 20.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Vilazodone (ITT Population), Placebo (ITT Population)
	Comments	Cochran-Mantel-Haenszel tests were used to compare MADRS remission rates between the treatment groups, stratifying by center. The asymptotic confidence interval of the risk difference was estimated by the normal approximation to the binomial distribution.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.066
	Comments
	Method	Cochran-Mantel-Haenszel
	Comments
Method of Estimation	Estimation Parameter	Risk Difference (RD)
	Estimated Value	0.069
	Confidence Interval	(2-Sided) 95%; -0.008 to 0.147
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	8 weeks
Arm/Group Title	Vilazodone (Safety Population)		Placebo (Safety Population)
Arm/Group Description	Vilazodone, 40mg		placebo to match vilazodone
All Cause Mortality
	Vilazodone (Safety Population)		Placebo (Safety Population)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Vilazodone (Safety Population)		Placebo (Safety Population)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	4/235 (1.7%)		2/233 (0.9%)
Cardiac disorders
Angina pectoris	1/235 (0.4%)	1	0/233 (0%)	0
General disorders
Chest pain	1/235 (0.4%)	1	0/233 (0%)	0
Hepatobiliary disorders
Cholecystitis	1/235 (0.4%)	1	0/233 (0%)	0
Infections and infestations
Pneumonia	1/235 (0.4%)	1	0/233 (0%)	0
Injury, poisoning and procedural complications
Ankle fracture	0/235 (0%)	0	1/233 (0.4%)	1
Nervous system disorders
Carotid arteriosclerosis	1/235 (0.4%)	1	0/233 (0%)	0
Respiratory, thoracic and mediastinal disorders
Asthma	0/235 (0%)	0	1/233 (0.4%)	2
Other (Not Including Serious) Adverse Events
	Vilazodone (Safety Population)		Placebo (Safety Population)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	148/235 (63%)		85/233 (36.5%)
Gastrointestinal disorders
Diarrhea	72/235 (30.6%)	91	25/233 (10.7%)	35
Dry Mouth	21/235 (8.9%)	21	9/233 (3.9%)	10
Nausea	61/235 (26%)	71	13/233 (5.6%)	15
Vomiting	12/235 (5.1%)	13	1/233 (0.4%)	2
Infections and infestations
Upper Respiratory Infections	8/235 (3.4%)	8	21/233 (9%)	21
Nervous system disorders
Dizziness	21/235 (8.9%)	21	9/233 (3.9%)	9
Headache	30/235 (12.8%)	32	24/233 (10.3%)	25
Psychiatric disorders
Abnormal Dreams	14/235 (6%)	14	4/233 (1.7%)	4
Insomnia	17/235 (7.2%)	22	7/233 (3%)	7

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The investigators have the right to publish or permit the publication of any information or material relating to or arising out of this protocol after prior submission to PGxHealth provided that, if PGxHealth requests, the investigator will delay publication for a maximum of six months to enable PGxHealth to protect their rights in such information or material.