Co-Administration of LDX (SPD489) and Venlafaxine XR (EFFEXOR XR) in Healthy Volunteers

Phase 1

Completed

• Conditions: Healthy
• Interventions: Drug: LDX + Venlafaxine XR; Drug: Venlafaxine XR + LDX

• Registration Number: NCT01235338
• Lead Sponsor: Shire

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-10-28
• Study First Submitted: 2010-11-02
• Study First Submitted QC: 2010-11-03
• Study First Posted: 2010-11-05
• Primary Completion: 2010-12-30
• Study Completion: 2011-01-17
• Results First Submitted: 2011-11-04
• Results First Submitted QC: 2011-11-04
• Results First Posted: 2011-12-08
• Status Verified: 2021-06
• Last Update Submitted: 2021-06-08
• Last Update Posted: 2021-06-14

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
LDX (SPD489) + Venlafaxine XR (Effexor XR)	LDX + Venlafaxine XR	-
Venlafaxine XR + LDX	Venlafaxine XR + LDX	-

Primary Outcome Measures

Name	Time	Method
Cmax of d-Amphetamine	Day 15 and Day 30 (24 hour sampling)	d-Amphetamine is the active isomer of Lisdexamfetamine dimesylate (SPD489) and is responsible for the drug's therapeutic activity.
Cmax of Composite (Venlafaxine + o-Desmethylvenlafaxine)	Day 15 and Day 30 (24 hour sampling)
AUC of Composite (Venlafaxine + o-Desmethylvenlafaxine)	Day 15 and Day 30 (24 hour sampling)
Tmax of d-Amphetamine	Day 15 and Day 30 (24 hour sampling)
Maximum Plasma Concentration (Cmax) of Lisdexamfetamine Dimesylate	Day 15 and Day 30 (24 hour sampling)	Lisdexamfetamine dimesylate (SPD489) itself is inactive, but following oral administration is converted to the active isomer, d-amphetamine, that is responsible for the drug's therapeutic activity.
Cmax of o-Desmethylvenlafaxine	Day 15 and Day 30 (24 hour sampling)	Venlafaxine, after oral administration, is metabolized in the liver to an active metabolite, o-Desmethylvenlafaxine.
AUC of Venlafaxine Hydrochloride	Day 15 and Day 30 (24 hour sampling)
Time of Maximum Plasma Concentration (Tmax) of Lisdexamfetamine Dimesylate	Day 15 and Day 30 (24 hour sampling)
Cmax of Venlafaxine Hydrochloride	Day 15 and Day 30 (24 hour sampling)	Venlafaxine Hydrochloride is the active ingredient of Effexor XR
Area Under the Steady-state Plasma Concentration-time Curve (AUC) of Lisdexamfetamine Dimesylate	Day 15 and Day 30 (24 hour sampling)
AUC of d-Amphetamine	Day 15 and Day 30 (24 hour sampling)
AUC of o-Desmethylvenlafaxine	Day 15 and Day 30 (24 hour sampling)
Tmax of Venlafaxine Hydrochloride	Day 15 and Day 30 (24 hour sampling)
Tmax of Composite (Venlafaxine + o-Desmethylvenlafaxine)	Day 15 and Day 30 (24 hour sampling)
Tmax of o-Desmethylvenlafaxine	Day 15 and Day 30 (24 hour sampling)

Secondary Outcome Measures

Name	Time	Method
Diastolic Blood Pressure	Baseline and up to 39 days
Pulse Rate	Baseline and up to 39 days
Systolic Blood Pressure	Baseline and up to 39 days

Trial Locations

Locations (1)

Clinical Pharmacology of Miami; 🇺🇸 Miami, Florida, United States