Clinical trial NCT01235338: Co-Administration of LDX (SPD489) and Venlafaxine XR (EFFEXOR XR) in Healthy Volunteers
Official title: A Phase 1, Open-label, Drug Interaction Study Evaluating the Pharmacokinetic Profiles of SPD489 and EFFEXOR XR, Administered Alone and in Combination in Healthy Adult Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Healthy
Lead sponsor: Takeda
Sponsor class: INDUSTRY
First posted: 2010-11-05
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study will examine the effects of co-administration of SPD489 and the antidepressant EFFEXOR XR on the pharmacokinetics of lisdexamfetamine, d-amphetamine, and EFFEXOR XR. In addition, serial blood pressure and pulse measures will be obtained and examined to ensure that there are no unexpected changes in vital signs following co administration of SPD489 and EFFEXOR XR that would impact the further study of this drug combination. The hypothesis is that a drug drug interaction could possibly exist.


Eligibility criteria: Inclusion Criteria:

1. Age 18-45 years
2. Subject is willing to comply with any applicable contraceptive requirements of the protocol and is:

   * Male, or
   * Non-pregnant, non-lactating female
   * Females must be at least 90 days post partum or nulliparous.
3. Female subjects must have a negative serum beta Human Chorionic Gonadotropin (HCG) pregnancy test
4. Satisfactory medical assessment
5. Ability to provide information on family history of hypertension.
6. Body Mass Index (BMI) between 18.5 and 30.0kg/m² inclusive.
7. Ability to swallow all investigational products.

Exclusion Criteria:

1. Current or recurrent disease (e.g., cardiovascular, renal, liver, gastrointestinal, malignancy or other conditions)
2. Current or relevant previous history of physical or psychiatric illness.
3. Significant illness.
4. History of significant anxiety, tension, or agitation as assessed by the Investigator.
5. History of or current diagnosis of glaucoma.
6. History of a seizure disorder (other than infantile febrile seizures), any tic disorder or a current diagnosis and/or known family history of Tourette's Disorder.
7. History of symptomatic cardiovascular disease, advanced arteriosclerosis, structural cardiac abnormality, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, transient ischemic attack or stroke, or other serious cardiac problems.
8. History of controlled or uncontrolled hypertension or a resting sitting systolic BP \>139mmHg or diastolic BP \>89mmHg.
9. Known family history of sudden cardiac death or ventricular arrhythmia.
10. Suicidal ideation or any lifetime history of suicidal behavior.
11. Consumption of alcohol, Seville oranges, grapefruit, or any grapefruit containing products within 7 days of first dose of investigational product.
12. Current use of any medication (including prescription, over the counter \[OTC\], herbal or homeopathic preparations or supplements) with the exception of the occasional dose of acetaminophen, or hormonal contraceptives.
13. History of alcohol or other substance abuse within the last year.
14. A positive screen for alcohol or drugs of abuse.
15. Male subjects who consume more than 21 units of alcohol per week or 3 units per day. Female subjects who consume more than 14 units of alcohol per week or 2 units per day. \[1 alcohol unit =1 beer = 1 wine (5oz) = 1 liquor (1.5oz) = 0.75oz alcohol\]
16. A positive human immunodeficiency virus (HIV) antibody screen, Hepatitis B surface antigen (HBsAg), or Hepatitis C virus (HCV) antibody screen.
17. Use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g. gum, patch). Ex-users must report that they have stopped using tobacco for at least 30 days prior to receiving the first dose of investigational product.
18. Routine consumption of more than 2 units of caffeine per day or subjects who experience caffeine withdrawal headaches. (One caffeine unit is contained in the following items: one 6oz. cup of coffee, two 12oz. cans of cola, one 12oz. cup of tea, three 1oz. chocolate bars, or one 8oz. serving of an energy drink. Decaffeinated coffee, tea, or cola are not considered to contain caffeine).
19. Donation of blood or blood products (e.g., plasma or platelets) within 60 days prior to receiving the first dose of investigational product.

Primary outcomes:
measure: Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Cmax of d-Amphetamine
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Cmax of Venlafaxine Hydrochloride
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Cmax of o-Desmethylvenlafaxine
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Cmax of Composite (Venlafaxine + o-Desmethylvenlafaxine)
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: AUC of d-Amphetamine
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: AUC of Venlafaxine Hydrochloride
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: AUC of o-Desmethylvenlafaxine
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: AUC of Composite (Venlafaxine + o-Desmethylvenlafaxine)
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Time of Maximum Plasma Concentration (Tmax) of Lisdexamfetamine Dimesylate
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Tmax of d-Amphetamine
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Tmax of Venlafaxine Hydrochloride
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Tmax of o-Desmethylvenlafaxine
timeFrame: Day 15 and Day 30 (24 hour sampling)
measure: Tmax of Composite (Venlafaxine + o-Desmethylvenlafaxine)
timeFrame: Day 15 and Day 30 (24 hour sampling)
Secondary outcomes:
measure: Systolic Blood Pressure
timeFrame: Baseline and up to 39 days
measure: Diastolic Blood Pressure
timeFrame: Baseline and up to 39 days
measure: Pulse Rate
timeFrame: Baseline and up to 39 days
Other outcomes:
Locations:
city: Miami
country: United States
facility: Clinical Pharmacology of Miami
state: Florida
Study officials:
affiliation: Takeda
name: Study Director
role: STUDY_DIRECTOR
References:
citation: Ermer J, Haffey MB, Richards C, Lasseter K, Roesch B, Purkayastha J, Corcoran M, Harlin B, Martin P. An open-label investigation of the pharmacokinetic profiles of lisdexamfetamine dimesylate and venlafaxine extended-release, administered alone and in combination, in healthy adults. Clin Drug Investig. 2013 Apr;33(4):243-54. doi: 10.1007/s40261-013-0073-1.